Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to ev...Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.展开更多
Objective:To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy(DR).Methods:172 Han subjects were selected from Xi’an Shaanxi Province;140 pat...Objective:To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy(DR).Methods:172 Han subjects were selected from Xi’an Shaanxi Province;140 patients with type 2 diabetes mellitus(T2DM)and 32 normal controls(NC)were selected from our hospital.Patients with diabetes were divided into a non-DR group(T2DM)(n=69)and a nonproliferative diabetic retinopathy Group(DR)(n=71)after dilated fundus photography and fundus fluorescein angiography.rs2110385/AluⅠgenotypes were detected by standardized polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and the differences in the detection rates of different genotypes in the above populations were compared.Results:1)The visfatin level in the DR Group was significantly higher than that in the NC and T2DM groups(P<0.05).2)The frequency of GG genotype and G allele of rs2110385 in the DR Group were higher than those in the T2DM and NC groups(80.3,69.6,50.0,86.6,79,65.6,P<0.05).3)There were significant differences in allele frequency and genotype frequency distribution of rs2110385 between the DR Group and the NC group(P<0.01).Conclusion:Visfatin increased in the nonproliferative diabetic retinopathy group and could be a potential indicator for the clinical prediction of DR.The G allele of the rs2110385 polymorphic site may be related to the risk of DR.展开更多
BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across dif...BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.展开更多
Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclea...Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.展开更多
Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
The growth hormone gene (GH) affects animal growth and is a potential target for genetic studies of variation related to growth traits. In this study, we analyzed single nucleotide polymorphisms (SNPs) in GH intron re...The growth hormone gene (GH) affects animal growth and is a potential target for genetic studies of variation related to growth traits. In this study, we analyzed single nucleotide polymorphisms (SNPs) in GH intron regions and their associations with growth traits in large yellow croaker, Larimichthys crocea, from Zhejiang and Fujian stocks. The results of PCR-single strand conformation polymorphism showed two haplotypes of intron 1, named AA and AB genotypes, in Zhejiang stock. AB exhibited an SNP at position 196 (G A) that was negatively correlated with body height and positively correlated with standard length/body height (P 0.05). Two different genotypes, CC and CD, were identified in intron 2 in Fujian stock, with CD showing an SNP at position 692 (T C). The CD genotype had a significantly positive correlation with both weight and total length (P 0.01). These basic data highlight the potential for using GH as a genetic marker of fish growth in marker assisted selection.展开更多
[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken a...[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken and porcine genomic sequence to amplify the 5＇ regulatory region of IGF-I, and the sequence was determined and analyzed. [ Result] A total of four SNPs were identified in this region by PCR-SSCP meth- od, that is, A to T at 26 nt, A to G at 215 nt, A to G at 314 nt, and A to T at 325 nt. [ Conclusioa] The two breeds ,wanxi white geese and Langde geese, agree with Hardy-weinberg equilibrium with respect to these SNPS.展开更多
Calpastatin is an endogenous inhibitor of calpain which is responsible for the breakdown of myofibrillar proteins, The association of Single Nucleotide Polymorphism （SNP） in the calpastatin gene with meat tenderness...Calpastatin is an endogenous inhibitor of calpain which is responsible for the breakdown of myofibrillar proteins, The association of Single Nucleotide Polymorphism （SNP） in the calpastatin gene with meat tenderness is an important topic in meat production. Therefore efficient procedure to investigate the SNP is necessary. The objectives of this study were to detect the SNP of calpastatin gene at domain L marker （G/C transversion） of the Kamphaengsaen beef breed （KPS cattle; n = 26） by the Amplification Refractory Mutation System （ARMS） compared with the Restriction Fragment Length Polymorphism （RFLP） methods and to determine the genotypes of the KPS cattle at that marker. Genomic DNA of calpastatin gene extracted from blood of the KPS cattle was detected with ARMS and RFLP methods. The ARMS system has utilized two primer pairs to amplify the two different alleles of a polymorphism in single PCR reaction to detected single base mutation. In this method, the alleles-specific primers had a mismatch at 3＇ terminal base and a second deliberate mismatch at position -2 from 3＇ terminus. While the RFLP method detected a polymorphism using PCR-base technique follow by RsaI restriction enzyme. Amplification of the ARMS method revealed that the results were not different from the conventional method of RFLP. Analysis of genotypes revealed that the KPS cattle inherited the CC, CG and GG genotypes at domain L marker. These were reliable when verified by nucleotide sequence analysis of PCR products. The animals were genotyped and determined for tenderness phenotype with this marker that predicted variation of an intronic polymorphism at domain L of the calpastatin gene. Therefore, the ARMS method was simple, efficient technique, and suitable for detecting SNP at domain L marker of the calpastatin gene.展开更多
Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe o...Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.展开更多
Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in th...Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.展开更多
Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of th...Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.展开更多
Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,o...Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.展开更多
With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genet...With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.展开更多
Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Si...Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators （SIRT1-7）. SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR （qPCR） indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNAsequencing, a total of three single nucleotide polymorphisms （SNPs） were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3＇ untranslated regions （UTR） of SIRT4 （SNP1： g. 13915A〉G） and two novel synonymous substitutions in SIRT7 （SNP2： g.3587C〉T and SNP3： g.3793T〉C）. Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.展开更多
AIM:To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltrans-ferase 3B(DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarci...AIM:To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltrans-ferase 3B(DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA). METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P=0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3B genotypes in GCA patents with or without lymphatic metastasis did not show significant difference (P= 0.42). CONCLUSION: The distribution of DNMT3B SNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.展开更多
Expression of estrogen receptors is correlated with breast cancer risk,but inconsistent results have been reported.To clarify potential estrogen receptor（ESR）-related breast cancer risk,we analyzed genetic variants ...Expression of estrogen receptors is correlated with breast cancer risk,but inconsistent results have been reported.To clarify potential estrogen receptor（ESR）-related breast cancer risk,we analyzed genetic variants of ESR1 in association with breast cancer susceptibility.We performed a meta-analysis to investigate the association between rs2234693,rs1801132,and rs2046210（single nucleotide polymorphisms of ESR1）,and breast cancer risk.Our analysis included 44 case-control studies.For rs2234693,the CC genotype had a higher risk of breast cancer compared to the TT or CT genotype.For rs2046210,the AA,GA,or GA ＋ GG genotype had a much higher risk compared to the GG genotype.No significant association was found for the rs 1801132 polymorphism with breast cancer risk.This meta-analysis demonstrates association between the rs2234693 and rs2046210 polymorphisms of ESR1 and breast cancer risk.The correlation strength between rs2234693 and breast cancer susceptibility differs in subgroup assessment by ethnicity.展开更多
AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at c...AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.展开更多
AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis fac...AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.展开更多
BACKGROUND Single nucleotide polymorphisms(SNPs)are universally present in nucleotide excision repair(NER)pathway genes,which could make impacts on colorectal carcinogenesis and prognosis.AIM To explore the associatio...BACKGROUND Single nucleotide polymorphisms(SNPs)are universally present in nucleotide excision repair(NER)pathway genes,which could make impacts on colorectal carcinogenesis and prognosis.AIM To explore the association of all tagSNPs in NER pathway genes with colorectal cancer(CRC)risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.METHODS Genotyping for NER SNPs was performed using kompetitive allele specific PCR.In the discovery stage,39 tagSNPs in eight genes were genotyped in 368 subjects,including 184 CRC cases and 184 individual-matched controls.In the validation stage,13 SNPs in six genes were analyzed in a total of 1712 subjects,including 854 CRC cases and 858 CRC-free controls.RESULTS Two SNPs(XPA rs10817938 and XPC rs2607775)were associated with an increased CRC risk in overall and stratification analyses.Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk.Another two SNPs(ERCC2 rs1052555 and ERCC5 rs2228959)were newly found to be associated with a poor overall survival of CRC patients.CONCLUSION Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population.The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.展开更多
Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A t...Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.展开更多
基金supported by grants from the Innovation and Cultivation Fund Project of the Seventh Medical Center,PLA General Hospital(No.QZX-2023-7)Postdoctoral Science Foundation of China(No.2021M691649)Postdoctoral Science Foundation of Jiangsu Province(No.2021K524C).
文摘Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.
基金Xi’an Science and Technology Bureau Fund(23YXYJ0103)Shaanxi Provincial Science and Technology Department Fund(S2022-YF-YBSF-0939).
文摘Objective:To investigate the association between rs2110385 polymorphisms of the visfatin gene and the risk of type 2 diabetic retinopathy(DR).Methods:172 Han subjects were selected from Xi’an Shaanxi Province;140 patients with type 2 diabetes mellitus(T2DM)and 32 normal controls(NC)were selected from our hospital.Patients with diabetes were divided into a non-DR group(T2DM)(n=69)and a nonproliferative diabetic retinopathy Group(DR)(n=71)after dilated fundus photography and fundus fluorescein angiography.rs2110385/AluⅠgenotypes were detected by standardized polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and the differences in the detection rates of different genotypes in the above populations were compared.Results:1)The visfatin level in the DR Group was significantly higher than that in the NC and T2DM groups(P<0.05).2)The frequency of GG genotype and G allele of rs2110385 in the DR Group were higher than those in the T2DM and NC groups(80.3,69.6,50.0,86.6,79,65.6,P<0.05).3)There were significant differences in allele frequency and genotype frequency distribution of rs2110385 between the DR Group and the NC group(P<0.01).Conclusion:Visfatin increased in the nonproliferative diabetic retinopathy group and could be a potential indicator for the clinical prediction of DR.The G allele of the rs2110385 polymorphic site may be related to the risk of DR.
基金Supported by the Natural Science Foundation for the Higher Education Institutions of Anhui Province of China,No.2023AH050561,No.2022AH051143,No.KJ2021A0266,and No.KJ2021A1228School-level offline courses,No.2021xjkc13.
文摘BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.
基金supported by grants from the National Natural Science Foundation of China,Nos. 81771216 (to JLP), 81520108010 (to BRZ),and 82101323 (to TS)the National Key R&D Program of China,No. 2018YFA0701400 (to HYL)+3 种基金the Primary Research and Development Plan of Zhejiang Province,No. 2020C03020 (to BRZ)the Key Project of Zhejiang Laboratory,No. 2018EB0ZX01 (to HYL)the Fundamental Research Funds for the Central Universities,No. 2019XZZX001-01-21 (to HYL)Preferred Foundation of Zhejiang Postdoctors,No. ZJ2021152 (to TS)。
文摘Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
基金Supported by the National Basic Research Program of China(973Program)(No.2010CB126304)the Special Fund for Agro-scientific Research in the Public Interest(No.200903046)the Project from the Ministry of Science and Technology of China(No.2006DKA30470017)
文摘The growth hormone gene (GH) affects animal growth and is a potential target for genetic studies of variation related to growth traits. In this study, we analyzed single nucleotide polymorphisms (SNPs) in GH intron regions and their associations with growth traits in large yellow croaker, Larimichthys crocea, from Zhejiang and Fujian stocks. The results of PCR-single strand conformation polymorphism showed two haplotypes of intron 1, named AA and AB genotypes, in Zhejiang stock. AB exhibited an SNP at position 196 (G A) that was negatively correlated with body height and positively correlated with standard length/body height (P 0.05). Two different genotypes, CC and CD, were identified in intron 2 in Fujian stock, with CD showing an SNP at position 692 (T C). The CD genotype had a significantly positive correlation with both weight and total length (P 0.01). These basic data highlight the potential for using GH as a genetic marker of fish growth in marker assisted selection.
文摘[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken and porcine genomic sequence to amplify the 5＇ regulatory region of IGF-I, and the sequence was determined and analyzed. [ Result] A total of four SNPs were identified in this region by PCR-SSCP meth- od, that is, A to T at 26 nt, A to G at 215 nt, A to G at 314 nt, and A to T at 325 nt. [ Conclusioa] The two breeds ,wanxi white geese and Langde geese, agree with Hardy-weinberg equilibrium with respect to these SNPS.
文摘Calpastatin is an endogenous inhibitor of calpain which is responsible for the breakdown of myofibrillar proteins, The association of Single Nucleotide Polymorphism （SNP） in the calpastatin gene with meat tenderness is an important topic in meat production. Therefore efficient procedure to investigate the SNP is necessary. The objectives of this study were to detect the SNP of calpastatin gene at domain L marker （G/C transversion） of the Kamphaengsaen beef breed （KPS cattle; n = 26） by the Amplification Refractory Mutation System （ARMS） compared with the Restriction Fragment Length Polymorphism （RFLP） methods and to determine the genotypes of the KPS cattle at that marker. Genomic DNA of calpastatin gene extracted from blood of the KPS cattle was detected with ARMS and RFLP methods. The ARMS system has utilized two primer pairs to amplify the two different alleles of a polymorphism in single PCR reaction to detected single base mutation. In this method, the alleles-specific primers had a mismatch at 3＇ terminal base and a second deliberate mismatch at position -2 from 3＇ terminus. While the RFLP method detected a polymorphism using PCR-base technique follow by RsaI restriction enzyme. Amplification of the ARMS method revealed that the results were not different from the conventional method of RFLP. Analysis of genotypes revealed that the KPS cattle inherited the CC, CG and GG genotypes at domain L marker. These were reliable when verified by nucleotide sequence analysis of PCR products. The animals were genotyped and determined for tenderness phenotype with this marker that predicted variation of an intronic polymorphism at domain L of the calpastatin gene. Therefore, the ARMS method was simple, efficient technique, and suitable for detecting SNP at domain L marker of the calpastatin gene.
基金Acknowledgment This work was supported by the National High Tech- nology Research and Development Program of China （Grants 2004AA216090 and 2002BA711A08）, National Basic Research Program of China （Grant 2004Cb518805）, the Natural National Science Foundation of China （Grant 30470960） and the China Medical Board of New York.
文摘Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.
基金supported by the Capital Development Fund Project (Grant No. 2002-1017).
文摘Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.
文摘Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.
文摘Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.
文摘With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.
基金supported by the National 863 Program of China (2013 AA102505)the National Natural Science Foundation of China (31272411 and 31402044)+2 种基金the National Beef and Yak Industrial Technology System,China (CARS-38)the China Postdoctoral Science Foundation (2016M590976)the Key Technologies R&D Program of Henan Province,China (122102110062)
文摘Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators （SIRT1-7）. SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR （qPCR） indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNAsequencing, a total of three single nucleotide polymorphisms （SNPs） were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3＇ untranslated regions （UTR） of SIRT4 （SNP1： g. 13915A〉G） and two novel synonymous substitutions in SIRT7 （SNP2： g.3587C〉T and SNP3： g.3793T〉C）. Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.
基金Supported by the National Natural Science Foundation of China,No.30371591the Natural Science Foundation of Hebei Province,No.C20040062
文摘AIM:To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltrans-ferase 3B(DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA). METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P=0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3B genotypes in GCA patents with or without lymphatic metastasis did not show significant difference (P= 0.42). CONCLUSION: The distribution of DNMT3B SNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.
基金supported by the National NaturalScience Foundation of China(No.81373102 to YZ,No.61301251 to LG)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.12KJB310003)+2 种基金Priority Academic Program Development of Jiangsu Higher Education Institution(PAPD)Flagship Major Development of Jiangsu Higher Education Institutionssupported by the Qing-lan Project of Jiangsu Province and the Excellent Young Teach Project of Nanjing Medical University
文摘Expression of estrogen receptors is correlated with breast cancer risk,but inconsistent results have been reported.To clarify potential estrogen receptor（ESR）-related breast cancer risk,we analyzed genetic variants of ESR1 in association with breast cancer susceptibility.We performed a meta-analysis to investigate the association between rs2234693,rs1801132,and rs2046210（single nucleotide polymorphisms of ESR1）,and breast cancer risk.Our analysis included 44 case-control studies.For rs2234693,the CC genotype had a higher risk of breast cancer compared to the TT or CT genotype.For rs2046210,the AA,GA,or GA ＋ GG genotype had a much higher risk compared to the GG genotype.No significant association was found for the rs 1801132 polymorphism with breast cancer risk.This meta-analysis demonstrates association between the rs2234693 and rs2046210 polymorphisms of ESR1 and breast cancer risk.The correlation strength between rs2234693 and breast cancer susceptibility differs in subgroup assessment by ethnicity.
文摘AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.
基金grant WS98-17 from the Netherlands Digestive Diseases Foundation
文摘AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.
基金Supported by the National Key R&D Program of China,No.2018YFC1311600
文摘BACKGROUND Single nucleotide polymorphisms(SNPs)are universally present in nucleotide excision repair(NER)pathway genes,which could make impacts on colorectal carcinogenesis and prognosis.AIM To explore the association of all tagSNPs in NER pathway genes with colorectal cancer(CRC)risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.METHODS Genotyping for NER SNPs was performed using kompetitive allele specific PCR.In the discovery stage,39 tagSNPs in eight genes were genotyped in 368 subjects,including 184 CRC cases and 184 individual-matched controls.In the validation stage,13 SNPs in six genes were analyzed in a total of 1712 subjects,including 854 CRC cases and 858 CRC-free controls.RESULTS Two SNPs(XPA rs10817938 and XPC rs2607775)were associated with an increased CRC risk in overall and stratification analyses.Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk.Another two SNPs(ERCC2 rs1052555 and ERCC5 rs2228959)were newly found to be associated with a poor overall survival of CRC patients.CONCLUSION Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population.The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.
文摘Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.
