Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-co...Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.展开更多
Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms.Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic...Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms.Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke.Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs.In this case-control study, we analyzed the distribution of prilet-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors.Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University.We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke.Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample.We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension.Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk.This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China(approval No.2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559) on December 27, 2017.展开更多
基金supported by the National Natural Science Foundation of China,No.81070913(to ZYH)
文摘Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.
基金supported by the National Natural Science Foundation of China, No.81901189the Natural Science Foundation of Liaoning Province of China, No.2019-BS-147(both to YZW)。
文摘Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms.Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke.Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs.In this case-control study, we analyzed the distribution of prilet-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors.Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University.We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke.Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample.We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension.Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk.This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China(approval No.2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559) on December 27, 2017.
