Huang Xiaoping, Li Ying, Huang Zhizheng, Wang Chun, Xu Zhenlin
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Jiangning District, Nanjing, 211166, Jiangsu, China.
J Mol Neurosci. 2014 Dec;54(4):803-10. doi: 10.1007/s12031-014-0418-0. Epub 2014 Sep 18.
Genetic variants of plasminogen activator inhibitor type 1 (PAI-1) gene have been suggested to influence the PAI-1 transcription activity and PAI-1 levels as well as might be involved in the pathophysiology of stroke. The aims of this study are to investigate whether the polymorphisms at the PAI-1 gene are associated with the risk of stroke and to explore the combined effects of PAI-1 variants and combined oral contraceptive (COC) use for stroke risk. We conducted a nested case-control study using 453 first-ever female stroke cases and 919 age- and region-matched controls that were recruited from our prospective surveillance cohort. SNP rs1799889 was genotyped by allele-specific polymerase chain reaction (PCR), and SNPs rs7242 and rs2227631 were detected by the TaqMan SNP genotyping assay. We identified that rs1799889 5G allele conferred a protective effect against ischemic stroke while 4G allele conferred an increased risk of ischemic stroke. But we failed to suggest associations of rs7242 and rs2227631. COC users had a 1.31-fold (OR=1.31, 95% CI=1.01-1.71) increased risk of stroke compared with the non-users. Furthermore, COC users with rs1799889 4G5G/5G5G genotype had a decreased risk of ischemic stroke (OR=0.53, 95% CI=0.34-0.83). Moreover, haplotype G-5G-T was associated with an increased risk of overall stroke (OR=1.28, 95% CI=1.01-1.62). In contrast, haplotype A-4G-G and haplotype G-5G-T were slightly associated with the protection from ischemic stroke (OR=0.61, 95% CI=0.46-0.82; OR=0.61, 95% CI=0.44-0.85, respectively). The study assessed the associations of three PAI-1 SNPs and also suggested combined effects of these PAI-1 gene variants and COC use on stroke risk in the Han Chinese women.
纤溶酶原激活物抑制剂1(PAI-1)基因的遗传变异被认为会影响PAI-1的转录活性和PAI-1水平,并且可能参与中风的病理生理过程。本研究的目的是调查PAI-1基因的多态性是否与中风风险相关,并探讨PAI-1变异与联合使用口服避孕药(COC)对中风风险的综合影响。我们进行了一项巢式病例对照研究,使用了从我们的前瞻性监测队列中招募的453例首次发生中风的女性病例和919例年龄及地区匹配的对照。通过等位基因特异性聚合酶链反应(PCR)对单核苷酸多态性(SNP)rs1799889进行基因分型,通过TaqMan SNP基因分型检测法检测SNP rs7242和rs2227631。我们发现rs1799889的5G等位基因对缺血性中风具有保护作用,而4G等位基因会增加缺血性中风的风险。但我们未发现rs7242和rs2227631存在关联。与未使用者相比,COC使用者中风风险增加1.31倍(比值比[OR]=1.31,95%置信区间[CI]=1.01-1.71)。此外,rs1799889 4G5G/5G5G基因型的COC使用者缺血性中风风险降低(OR=0.53,95% CI=0.34-0.83)。而且,单倍型G-5G-T与总体中风风险增加相关(OR=1.28,95% CI=1.01-1.62)。相比之下,单倍型A-4G-G和单倍型G-5G-T与预防缺血性中风略有关联(分别为OR=0.61,95% CI=0.46-0.82;OR=0.61,95% CI=0.44-0.85)。该研究评估了三个PAI-1 SNP的关联,并提示了这些PAI-1基因变异与COC使用对中国汉族女性中风风险的综合影响。