Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nin...Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.展开更多
Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 1...Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 153 unrelated individuals of Chinese Han population in Shaanxi province. Allele and genotype frequencies for the 6 STR loci were estimated and statistical parameters of polymorphism were calculated. Results 8 alleles and 18 genotypes, 10 alleles and 17 genotypes, 9 alleles and 15 genotypes, 12alleles and 29 genotypes, 12 alleles and 31 genotypes, 8 alleles and 11 genotypes were observed at D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613, respectively. No deviations of the observed allele frequency from Hardy-weinberg equilibrium expectations were found for any of these loci. The Heterozygotes of these 6 loci were 78.89%, 66.10%, 54.95%, 79.10%, 71.98% and 59.48%, respectively. It indicated the high genetic polymorphism of the loci in Chinese Han population. Conclusion The 6 STR loci belonged to the genetic marker system of high discriminutesation and high information in Chinese Han population and can be used in the study of gene-related diseases.展开更多
Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese ch...Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese children ,and analyzed the association between the 5-HTTLPR and clinical symptoms of the Han Chinese children with CA. Methods Genomic DNAs of fifty subjects including 25 autistic children and 25 controls were extracted from blood samples. PCR amplification using Oligonucleotide primers flanking 5-HTTLPR was performed. Results ① Three kinds of alleles including the S (short) allele, the L (long) allele and the VL allele were found , and the 5-HTTLPR genotypes shown were S/S, L/L, S/L and L/VL. ② Allele frequencies did not differ significantly in patient groups in comparison with the control sample. No significant difference was identified between the observed 5-HTTLPR genotype distribution of the patient groups and control group. ③ The distribution of homozygous and heterozygous subjects between the two groups differed significantly. ④ The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor. ⑤ The allele frequency of healthy Han Chinese population and that of healthy Japanese population were similar. The frequency of S allele in not only autistic subjects but also healthy children in this study was considerably more than that in Caucasians and the frequency of L allele in our subjects decreased correspondingly. Conclusion ① A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found. ② The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor of the patients. ③ The homozygote and the L allele were positively relevant to CA and they might be the risk factors of CA. The heterozygote and the S allele were negatively relevant to CA and they might be the protective factors of CA.展开更多
While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from t...While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.展开更多
Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipient...Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-展开更多
Neuroinflammatory processes are a central feature of Alzheimer's disease(AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the...Neuroinflammatory processes are a central feature of Alzheimer's disease(AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro- and anti-inflammatory cytokines related to AD, primarily interleukin-1(IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.展开更多
Infertility affects about 15%of the world's population.In 40%-50%of infertile couples,a male factor underlies the problem,but in about 50%of these cases,the etiology of male infertility remains unexplained.Some cl...Infertility affects about 15%of the world's population.In 40%-50%of infertile couples,a male factor underlies the problem,but in about 50%of these cases,the etiology of male infertility remains unexplained.Some clinical data show that lifestyle interventions may contribute to male reproductive health.Cessation of unhealthy habits is suggested for preserving male fertility;there is growing evidence that most preexisting comorbidities,such as obesity and metabolic syndrome,are highly likely to have an impact on male fertility.The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility.Although these polymorphisms are not directly connected with male infertility,they may have a role in specific conditions associated with it,that is,metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage.Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility,but their results have not been synthesized.We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation,by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.展开更多
X chromosomal short tandem repeats(X-STRs)have the characteristics of both autosomal and uniparental genetic markers and have been shown to be particularly useful in forensic casework.However,relevant research or repo...X chromosomal short tandem repeats(X-STRs)have the characteristics of both autosomal and uniparental genetic markers and have been shown to be particularly useful in forensic casework.However,relevant research or reports have not focused on X-STRs in the Hani population.To investigate the genetic variation and forensic efficiency of 16 X-STR loci in the Hani ethnic minority,we calculated the allele frequencies and forensic parameters of 451(116 males and 335 females)unrelated healthy Hani individuals from Yunnan Province,Southwest China.All these loci are highly polymorphic in Hani individuals in Yunnan Province except DXS6800.The combined power of discrimination in males(PDM)and power of discrimination in females(PDF)were found to be 0.999999998433993 and 0.999999999999998,respectively.Furthermore,a population genetic structure investigation between the Yunnan Hani population and another 18 populations was performed using a principal component analysis,multidimensional scaling plot and neighbouring-joining phylogenetic tree and the findings illustrated that neighbouring populations and different nationalities in the same area appeared to have a closer evolutionary relationship.This study provides the first batch of X chromosome genetic polymorphism data of the Hani population in Yunnan Province,Southwest China and enriches the reference database of the Chinese minority population.展开更多
Natural genetic polymorphisms are gifts from nature and sources of variations at all levels.The postgenomic era permits new perspectives on interpreting genetic polymorphisms and also poses challenges for scientists t...Natural genetic polymorphisms are gifts from nature and sources of variations at all levels.The postgenomic era permits new perspectives on interpreting genetic polymorphisms and also poses challenges for scientists to answer system questions.Rather than a comprehensive coverage of genetic polymorphisms upto-date,this review attempts to present some of the results in a somewhat coherent manner to highlight the needs and potentials of pertinent studies.展开更多
To investigate the genetic polymorphisms of 19 X‑STR loci in the Han population in Northern China,samples from 628 unrelated individuals(314 males and 314 females)were collected and 19 X‑STR loci were amplified by AGC...To investigate the genetic polymorphisms of 19 X‑STR loci in the Han population in Northern China,samples from 628 unrelated individuals(314 males and 314 females)were collected and 19 X‑STR loci were amplified by AGCU X19 STR System.A total of 270 different alleles were detected in 19 X‑STR loci.All loci were in Hardy−Weinberg equilibrium and there was only one pair of linkage loci(DXS10103‑DXS10101).There was no significant difference in allele frequency between male and female populations.The combined power of discrimination in males was 1–1.8667×10−13,while the combined power of discrimination in females was 1–3.6532×10−22.The combined mean paternity exclusion chance(CMEC)for X-chromosomal markers in father/daughter or mother/son duos Mean paternity exclusion chance(MECDesmarais Duo)was 1–5.1109×10−9.Moreover,the CMEC for X-chromosomal markers in trios involving daughters(MECDesmarais)was 1–2.0292×10−12.The compound amplification system composed of 19 X‑STR in this study showed high polymorphism in the Han population of Northern China,which had a high application value in difficult genetic relationship identification.展开更多
Goldeneye™DNA ID 22NC Kit is a novel short tandem repeat(STR)genotyping system that investigate 20 non-CODIS loci(D4S2366,D6S477,D22GATA198B05,D15S659,D8S1132,D3S3045,D14S608,D17S1290,D3S1744,D2S441,D18S535,D13S325,D7...Goldeneye™DNA ID 22NC Kit is a novel short tandem repeat(STR)genotyping system that investigate 20 non-CODIS loci(D4S2366,D6S477,D22GATA198B05,D15S659,D8S1132,D3S3045,D14S608,D17S1290,D3S1744,D2S441,D18S535,D13S325,D7S1517,D1OS1435,D11S236&D19S253,D1S1656,D7S3O4&D10S14&and D5S2500),a CODIS locus(D3S1358),and a sex-determining locus amelogenin in one assay.In the present study,this STR genotyping system was validated according to the guidelines of"Wlidation Guidelines for DNA Analysis Methods(2016)"updated by the Scientific Working Group on DNA Analysis Methods.A series of tests,such as polymerase chain reaction-based studies,sensitivity,inhibitors,DNA mixture,species specificity,precision and accuracy evaluation,stutter percentage,and peak height ratio,was conducted.The genetic polymorphism of 21 STR loci that included in the 22NC system was also investigated in the Chinese Hunan Han population.The validation results demonstrated that Goldeneye™DNA ID 22NC Kit is a robust and reliable identification assay as required for genotyping in kinship analysis and forensic investigation.The 21 STR loci in this kit also showed a high level of genetic polymorphism for the Hunan Han population.Therefore,it can be used for forensic applications and population studies.展开更多
Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the v...Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.展开更多
Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual ...Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2<Abstract>Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among popula- tions. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo- denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations..02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo-denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.展开更多
AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patien...AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays.RESULTS:The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR:0.14,95% CI:0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR:5.04,95% CI:1.43-17.8).CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs 708272 polymorphisms may be related to the risk of developing GBC in Chilean women.展开更多
AIM:To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.METHODS: Twelve Finnish patient...AIM:To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.METHODS: Twelve Finnish patients with autoimmunetype severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen-interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon γ, transforming growth factor β, and tumor necrosis factor α. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations.RESULTS: All patients had pepsinogen-CONCLUSION: As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.展开更多
AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospect...AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction(PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A-1498C>T(rs833031) and-634G>C(rs2010963) polymorphisms. Genotyping was validated for VEGF-A-1498C>T polymorphism in 129 patients and for VEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association(OR = 0.32; P = 0.048) between genotype CC of the VEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A-1498C>T polymorphism and VEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival(P = 0.032), but not significant difference(P = 0.27) was obtained with the VEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT(HR = 2.79) and CC(HR = 4.67) of the polymorphism VEGF-A-1498C>T and the genotype CC(HR = 3.76) of the polymorphism VEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A-1498C>T and the CC genotype of the VEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.展开更多
BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persiste...BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.展开更多
Context:As the increasing number of pet canines,the identification of canine has attracted much attentions in the forensic field,however,the genetic diversities of pet canines still remained unknown.Aims:To explore ge...Context:As the increasing number of pet canines,the identification of canine has attracted much attentions in the forensic field,however,the genetic diversities of pet canines still remained unknown.Aims:To explore genetic polymorphisms of 19 short tandem repeat(STR)loci and genetic relationships between the two studied canine groups and reference group.Subjects and Methods:In the present study,genetic polymorphisms of 19 STR loci and a sex-linked zinc finger locus were analyzed in a total of 594 canines in Standard Poodle and Bichon Frise groups from China.Results:A total of 166,159 alleles were observed in the Standard Poodle,Bichon Frise groups with the corresponding allelic frequencies ranging from 0.0030-0.6108 to 0.0012-0.6148,respectively.The combined discrimination power and probability of exclusion of 19 STR loci in Standard Poodle and Bichon Frise groups were 0.9999999999999497,0.999962884;and 0.99999999999999995,0.999965955,respectively.Furthermore,the genetic distances between the two canine groups and Labrador retriever group were calculated,and the results indicated that Standard Poodle and Bichon Frise groups showed a closer genetic relationship,while the two canine groups had distant genetic relationships with Labrador retriever group.The result of population genetic structure revealed that genetic component distributions in the three canine groups were different.The predicted accuracies of the constructed random forest prediction model for three validation sets(25%individuals randomly selected from three populations with 808 individuals)were higher than 0.9,especially for the individuals in validation set from the Bichon Frise group is 1.Conclusions:The 19 STR loci could be used for individual identification,canine breed identification and paternity testing in the two canine groups.展开更多
Objective:To investigate 38 Y-chromosome short tandem repeat(Y-STR)genetic polymorphisms in Beijing Han and analyze the genetic distance with neighboring or linguistically similar populations.Materials and Methods:In ...Objective:To investigate 38 Y-chromosome short tandem repeat(Y-STR)genetic polymorphisms in Beijing Han and analyze the genetic distance with neighboring or linguistically similar populations.Materials and Methods:In the study,we selected 531 unrelated male individuals of Beijing Han,and the results were statistically analyzed by testing with GSTAR™41Y reagents.Results:The allele peak heights were balanced among the Y loci,the amplified fragment ranged from 100 to 500 bps.A total of 531 haplotypes were detected in 531 samples.Eight null genotypes were observed on locus DYS448.One and three double alleles were observed on single-copy locus DYS576 and DYS19,respectively.DYS385 a/b,DYF387S1 a/b,and DYS527 a/b were more common in double copies,but 3,13,and 11 triple alleles were detected,respectively.The gene diversity values of Y-STRs except DYS391,DYS438,and DYS645 were>0.5.Twenty-seven Y-STRs of Beijing Han population were selected for genetic distance comparison with 17 populations including Changchun Han,with Rst values ranging from 0.0002 to 0.1703.Conclusion:The 38 Y-STRs in this study have strong male lineage identification ability and have great potential for individual identification,kinship identification,Y-STR database construction,and genetic relationship research.展开更多
AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 inserti...AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We identified 8 studies (6439 cases and 4798 controls) in Caucasian populations using PubMed search. We found no association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease, Crohn's disease, and ulcerative colitis. Stratification of cases by age showed that NOD1/CARD4 insertion/deletion polymorphism was associated with inflammatory bowel disease in younger age group at onset (< 40 years) (GG vs T: OR = 0.68, 95% CI: 0.50-0.93, P = 0.02; GG/T + GG/GG vs T/T: OR = 0.71, 95% CI: 0.59-0.85, P = 0.0003). CONCLUSION: This meta-analysis demonstrates an association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease in the younger age group at onset (< 40 years) in Caucasian populations.展开更多
文摘Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.
文摘Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 153 unrelated individuals of Chinese Han population in Shaanxi province. Allele and genotype frequencies for the 6 STR loci were estimated and statistical parameters of polymorphism were calculated. Results 8 alleles and 18 genotypes, 10 alleles and 17 genotypes, 9 alleles and 15 genotypes, 12alleles and 29 genotypes, 12 alleles and 31 genotypes, 8 alleles and 11 genotypes were observed at D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613, respectively. No deviations of the observed allele frequency from Hardy-weinberg equilibrium expectations were found for any of these loci. The Heterozygotes of these 6 loci were 78.89%, 66.10%, 54.95%, 79.10%, 71.98% and 59.48%, respectively. It indicated the high genetic polymorphism of the loci in Chinese Han population. Conclusion The 6 STR loci belonged to the genetic marker system of high discriminutesation and high information in Chinese Han population and can be used in the study of gene-related diseases.
文摘Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese children ,and analyzed the association between the 5-HTTLPR and clinical symptoms of the Han Chinese children with CA. Methods Genomic DNAs of fifty subjects including 25 autistic children and 25 controls were extracted from blood samples. PCR amplification using Oligonucleotide primers flanking 5-HTTLPR was performed. Results ① Three kinds of alleles including the S (short) allele, the L (long) allele and the VL allele were found , and the 5-HTTLPR genotypes shown were S/S, L/L, S/L and L/VL. ② Allele frequencies did not differ significantly in patient groups in comparison with the control sample. No significant difference was identified between the observed 5-HTTLPR genotype distribution of the patient groups and control group. ③ The distribution of homozygous and heterozygous subjects between the two groups differed significantly. ④ The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor. ⑤ The allele frequency of healthy Han Chinese population and that of healthy Japanese population were similar. The frequency of S allele in not only autistic subjects but also healthy children in this study was considerably more than that in Caucasians and the frequency of L allele in our subjects decreased correspondingly. Conclusion ① A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found. ② The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor of the patients. ③ The homozygote and the L allele were positively relevant to CA and they might be the risk factors of CA. The heterozygote and the S allele were negatively relevant to CA and they might be the protective factors of CA.
文摘While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.
文摘Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-
基金partly supported by the National Natural Science Foundation of China (91332104 and 81201080)the Program for New Century Excellent Talents in University, China (NCET-13-0117)+4 种基金the Key Program for Clinical Medicine and Science and Technology of Jiangsu Province Clinical Medical Research Center, China (BL2013025)the Natural Science Foundation of Jiangsu Province, China (BK2012337)the National High-Tech R&D Program (863 Program) of China (SQ2015AA0200064)the Doctoral Fund of the Ministry of Education of China (20120092120068)the Graduate Candidate Research Innovation Program of Jiangsu Province, China (KYLX15_0188)
文摘Neuroinflammatory processes are a central feature of Alzheimer's disease(AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro- and anti-inflammatory cytokines related to AD, primarily interleukin-1(IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.
文摘Infertility affects about 15%of the world's population.In 40%-50%of infertile couples,a male factor underlies the problem,but in about 50%of these cases,the etiology of male infertility remains unexplained.Some clinical data show that lifestyle interventions may contribute to male reproductive health.Cessation of unhealthy habits is suggested for preserving male fertility;there is growing evidence that most preexisting comorbidities,such as obesity and metabolic syndrome,are highly likely to have an impact on male fertility.The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility.Although these polymorphisms are not directly connected with male infertility,they may have a role in specific conditions associated with it,that is,metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage.Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility,but their results have not been synthesized.We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation,by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.
基金This work was supported by the National Natural Science Foundation of China[grant numbers 81860258 and 31860300]Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University[grant numbers 2017FE467(-022),2018FE001(-131)and 2019FE001(-011)]+3 种基金Yunnan Educational Science Foundation program[grant numbers 2018JS170 and 2018JS171]Yunnan Provincial Young Academic and Technical Leader Reserve Talent Project[grant number 2018HB104]Hundred-Talent Program of Kunming Medical University[grant number 60117190447]Science and Technology Innovation Group of Kunming Medical University[grant number CXTD201803].
文摘X chromosomal short tandem repeats(X-STRs)have the characteristics of both autosomal and uniparental genetic markers and have been shown to be particularly useful in forensic casework.However,relevant research or reports have not focused on X-STRs in the Hani population.To investigate the genetic variation and forensic efficiency of 16 X-STR loci in the Hani ethnic minority,we calculated the allele frequencies and forensic parameters of 451(116 males and 335 females)unrelated healthy Hani individuals from Yunnan Province,Southwest China.All these loci are highly polymorphic in Hani individuals in Yunnan Province except DXS6800.The combined power of discrimination in males(PDM)and power of discrimination in females(PDF)were found to be 0.999999998433993 and 0.999999999999998,respectively.Furthermore,a population genetic structure investigation between the Yunnan Hani population and another 18 populations was performed using a principal component analysis,multidimensional scaling plot and neighbouring-joining phylogenetic tree and the findings illustrated that neighbouring populations and different nationalities in the same area appeared to have a closer evolutionary relationship.This study provides the first batch of X chromosome genetic polymorphism data of the Hani population in Yunnan Province,Southwest China and enriches the reference database of the Chinese minority population.
基金supported by grants from the Chinese Academy of Sciences(No.171846).
文摘Natural genetic polymorphisms are gifts from nature and sources of variations at all levels.The postgenomic era permits new perspectives on interpreting genetic polymorphisms and also poses challenges for scientists to answer system questions.Rather than a comprehensive coverage of genetic polymorphisms upto-date,this review attempts to present some of the results in a somewhat coherent manner to highlight the needs and potentials of pertinent studies.
文摘To investigate the genetic polymorphisms of 19 X‑STR loci in the Han population in Northern China,samples from 628 unrelated individuals(314 males and 314 females)were collected and 19 X‑STR loci were amplified by AGCU X19 STR System.A total of 270 different alleles were detected in 19 X‑STR loci.All loci were in Hardy−Weinberg equilibrium and there was only one pair of linkage loci(DXS10103‑DXS10101).There was no significant difference in allele frequency between male and female populations.The combined power of discrimination in males was 1–1.8667×10−13,while the combined power of discrimination in females was 1–3.6532×10−22.The combined mean paternity exclusion chance(CMEC)for X-chromosomal markers in father/daughter or mother/son duos Mean paternity exclusion chance(MECDesmarais Duo)was 1–5.1109×10−9.Moreover,the CMEC for X-chromosomal markers in trios involving daughters(MECDesmarais)was 1–2.0292×10−12.The compound amplification system composed of 19 X‑STR in this study showed high polymorphism in the Han population of Northern China,which had a high application value in difficult genetic relationship identification.
基金the National Natural Science Foundation of China(No.81302615,81302621,and 81571855).
文摘Goldeneye™DNA ID 22NC Kit is a novel short tandem repeat(STR)genotyping system that investigate 20 non-CODIS loci(D4S2366,D6S477,D22GATA198B05,D15S659,D8S1132,D3S3045,D14S608,D17S1290,D3S1744,D2S441,D18S535,D13S325,D7S1517,D1OS1435,D11S236&D19S253,D1S1656,D7S3O4&D10S14&and D5S2500),a CODIS locus(D3S1358),and a sex-determining locus amelogenin in one assay.In the present study,this STR genotyping system was validated according to the guidelines of"Wlidation Guidelines for DNA Analysis Methods(2016)"updated by the Scientific Working Group on DNA Analysis Methods.A series of tests,such as polymerase chain reaction-based studies,sensitivity,inhibitors,DNA mixture,species specificity,precision and accuracy evaluation,stutter percentage,and peak height ratio,was conducted.The genetic polymorphism of 21 STR loci that included in the 22NC system was also investigated in the Chinese Hunan Han population.The validation results demonstrated that Goldeneye™DNA ID 22NC Kit is a robust and reliable identification assay as required for genotyping in kinship analysis and forensic investigation.The 21 STR loci in this kit also showed a high level of genetic polymorphism for the Hunan Han population.Therefore,it can be used for forensic applications and population studies.
文摘Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.
文摘Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2<Abstract>Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among popula- tions. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo- denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations..02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo-denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.
基金Supported by (in part) A Grant-in-Aid for Scientific Research (C) (2007,#19590582) from the Japanese Ministry of Education,Science,Sports and Culture
文摘AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays.RESULTS:The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR:0.14,95% CI:0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR:5.04,95% CI:1.43-17.8).CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs 708272 polymorphisms may be related to the risk of developing GBC in Chilean women.
基金Supported by A grant from the Research Unit of the Health Centre,City of Helsinki
文摘AIM:To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.METHODS: Twelve Finnish patients with autoimmunetype severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen-interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon γ, transforming growth factor β, and tumor necrosis factor α. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations.RESULTS: All patients had pepsinogen-CONCLUSION: As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.
文摘AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction(PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A-1498C>T(rs833031) and-634G>C(rs2010963) polymorphisms. Genotyping was validated for VEGF-A-1498C>T polymorphism in 129 patients and for VEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association(OR = 0.32; P = 0.048) between genotype CC of the VEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A-1498C>T polymorphism and VEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival(P = 0.032), but not significant difference(P = 0.27) was obtained with the VEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT(HR = 2.79) and CC(HR = 4.67) of the polymorphism VEGF-A-1498C>T and the genotype CC(HR = 3.76) of the polymorphism VEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A-1498C>T and the CC genotype of the VEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.
基金Supported by Chang Gung Memorial Hospital,No.CMRPG3C0701and National Science Council,No.NSC101-2314-B-182A-025-MY3 and No.MOST 107-2314-B-039-059.
文摘BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.
基金supported by Shaanxi Science and Technology Co‑ordination and Innovation Project under Grant(number 2015KTCL03‑03)。
文摘Context:As the increasing number of pet canines,the identification of canine has attracted much attentions in the forensic field,however,the genetic diversities of pet canines still remained unknown.Aims:To explore genetic polymorphisms of 19 short tandem repeat(STR)loci and genetic relationships between the two studied canine groups and reference group.Subjects and Methods:In the present study,genetic polymorphisms of 19 STR loci and a sex-linked zinc finger locus were analyzed in a total of 594 canines in Standard Poodle and Bichon Frise groups from China.Results:A total of 166,159 alleles were observed in the Standard Poodle,Bichon Frise groups with the corresponding allelic frequencies ranging from 0.0030-0.6108 to 0.0012-0.6148,respectively.The combined discrimination power and probability of exclusion of 19 STR loci in Standard Poodle and Bichon Frise groups were 0.9999999999999497,0.999962884;and 0.99999999999999995,0.999965955,respectively.Furthermore,the genetic distances between the two canine groups and Labrador retriever group were calculated,and the results indicated that Standard Poodle and Bichon Frise groups showed a closer genetic relationship,while the two canine groups had distant genetic relationships with Labrador retriever group.The result of population genetic structure revealed that genetic component distributions in the three canine groups were different.The predicted accuracies of the constructed random forest prediction model for three validation sets(25%individuals randomly selected from three populations with 808 individuals)were higher than 0.9,especially for the individuals in validation set from the Bichon Frise group is 1.Conclusions:The 19 STR loci could be used for individual identification,canine breed identification and paternity testing in the two canine groups.
基金supported by opening research grants from Shanghai Key Lab of Forensic Medicine,Key Lab of Forensic Science,Ministry of Justice,PR.China(Academy of Forensic Science)(No.KF202111)supported by the Fundamental Research Funds for the Central Universities.
文摘Objective:To investigate 38 Y-chromosome short tandem repeat(Y-STR)genetic polymorphisms in Beijing Han and analyze the genetic distance with neighboring or linguistically similar populations.Materials and Methods:In the study,we selected 531 unrelated male individuals of Beijing Han,and the results were statistically analyzed by testing with GSTAR™41Y reagents.Results:The allele peak heights were balanced among the Y loci,the amplified fragment ranged from 100 to 500 bps.A total of 531 haplotypes were detected in 531 samples.Eight null genotypes were observed on locus DYS448.One and three double alleles were observed on single-copy locus DYS576 and DYS19,respectively.DYS385 a/b,DYF387S1 a/b,and DYS527 a/b were more common in double copies,but 3,13,and 11 triple alleles were detected,respectively.The gene diversity values of Y-STRs except DYS391,DYS438,and DYS645 were>0.5.Twenty-seven Y-STRs of Beijing Han population were selected for genetic distance comparison with 17 populations including Changchun Han,with Rst values ranging from 0.0002 to 0.1703.Conclusion:The 38 Y-STRs in this study have strong male lineage identification ability and have great potential for individual identification,kinship identification,Y-STR database construction,and genetic relationship research.
基金Supported by The National Natural Science Foundation of China (30972530)
文摘AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We identified 8 studies (6439 cases and 4798 controls) in Caucasian populations using PubMed search. We found no association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease, Crohn's disease, and ulcerative colitis. Stratification of cases by age showed that NOD1/CARD4 insertion/deletion polymorphism was associated with inflammatory bowel disease in younger age group at onset (< 40 years) (GG vs T: OR = 0.68, 95% CI: 0.50-0.93, P = 0.02; GG/T + GG/GG vs T/T: OR = 0.71, 95% CI: 0.59-0.85, P = 0.0003). CONCLUSION: This meta-analysis demonstrates an association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease in the younger age group at onset (< 40 years) in Caucasian populations.
