过氧化物酶体增殖剂激活受体γ基因多态性对缺血性脑卒中发生风险影响的前瞻性研究

A prospective study on the effects of PPARγgene polymorphisms on the risk of ischemic stroke

目的评估过氧化物酶体增殖剂激活受体γ(PPARγ)基因单核苷酸多态性(SNP)与缺血性脑卒中(IS)发生风险的前瞻性关联,为IS的预防和控制提供新思路。方法研究对象来源于苏州工业园区慢性病防治前瞻性队列研究(135项目)。2013年按照纳入、排除标准选取1569名研究对象完成基线调查,2016年进行第1次随访调查,调查项目包括问卷调查、体格检查及血样本采集,以2016年12月31日作为本研究随访的终点。对1569名研究对象进行PPARγ基因rs3856806、rs13433696和rs9817428位点的分型。使用R 3.6.2的SNPassoc包分析所选SNP与发生IS风险之间的前瞻性关联。使用SAS 9.4软件进行Cox比例风险模型分析基因-血压的联合作用。结果在4年的随访中,共58人发生IS(3.70%)。rs3856806、rs13433696和rs9817428位点与IS发生风险的直接关联无统计学意义(P>0.05)。与携带rs3856806位点CC基因型的非高血压人群相比,携带CC基因型的高血压患者发生IS的风险是其3.24倍(95%CI:1.48~7.11),携带CT或TT基因型的高血压患者发生IS的风险是其3.92倍(95%CI:1.76~8.70)。与携带rs13433696位点GG基因型的非高血压人群相比,携带GG基因型的高血压患者发生IS的风险是其5.01倍(95%CI:1.84~13.61),携带GA或AA基因型的高血压患者发生IS的风险是其4.72倍(95%CI:1.79~12.50)。与携带rs9817428 AA位点的非高血压人群相比,携带该位点AC或CC基因型的高血压患者发生IS的风险是其3.81倍(95%CI:1.48~9.79),且携带rs9817428位点AC或CC基因型且收缩压(SBP)≥140 mm Hg的患者发生IS风险是携带rs9817428位点AA基因型且SBP<140 mm Hg人群的2.36倍(95%CI:1.09~5.13)。rs3856806、rs13433696位点与SBP或DBP的联合作用与IS发生风险的关联均无统计学意义(P>0.05)。结论携带rs9817428位点突变基因型的高血压患者发生IS的风险增加。

Objective To evaluate the prospective association of single nucleotide polymorphisms(SNPs)in peroxisome proliferative activated receptor-gamma gene(PPARγ)with the risk of ischemic stroke(IS),and provide the new ideas for the prevention and control of IS.Methods The subjects were from the prospective cohort study of chronic disease prevention and control in Suzhou Industrial Park(135 project).In 2013,1569 subjects were selected according to the inclusion and exclusion criteria to complete the baseline investigation,and the first follow-up was conducted in 2016.The investigation items included the questionnaire survey,physical examination and blood sample collection.December 31,2016 served as the end point of the follow-up of this study.The polymorphisms of rs3856806,rs13433696 and rs9817428 of PPARγgene were genotyped in 1569 subjects.The prospective association of the selected SNPs with the risk of IS was analyzed using SNPassoc package of R language 3.6.2,and SAS9.4 was used to analyze the joint effect of gene-hypertension using the Cox proportional hazard model.Results During four years of follow-up,58 cases(3.70%)developed IS.The direct association of rs3856806,rs13433696 and rs9817428 polymorphisms with the risk of IS was not statistically significant(P>0.05).As compared with non-hypertensive population with rs3856806 CC genotype,the hypertensive patients with CC genotype had a 3.24 times higher risk of IS(95%CI:1.48-7.11),and the hypertensive patients with CT or TT genotype had a 3.92 times higher risk of IS(95%CI:1.76-8.70).As compared with non-hypertensive population with rs13433696 GG genotype,the hypertensive patients with rs13433696 GG genotype had a 5.01 times higher risk of IS(95%CI:1.84-13.61),and the hypertensive patients with GA or AA genotype had a 4.72 times higher risk of IS(95%CI:1.79-12.50).As compared with non-hypertensive population with rs9817428 AA genotype,the hypertensive patients with AC or CC genotype had a 3.81times higher risk of IS(95%CI:1.48-9.79).The risk of IS in patients with rs9817428 AC or CC genotype and systolic blood pressure(SBP)≥140 mm Hg was 2.36 times higher than that in participants with rs9817428 AA genotype and SBP<140 mm Hg(95%CI:1.09-5.13).The combined effects of rs3856806 and rs13433696 with SBP or DBP were not significantly associated with the risk of IS(P>0.05).Conclusion The study indicates that hypertension patients with mutated genotypes of rs9817428 in PPARγhave high risk of IS.