C反应蛋白基因多态性与超敏C反应蛋白的关系及其与缺血性脑卒中的关联研究

摘要

目的 探讨C反应蛋白(CRP)基因多态性与血浆超敏C反应蛋白(hs-CRP)水平的关系并分析其对缺血性脑卒中(IS)遗传易感性的影响.方法 采用病例对照研究方法,以2008年1月至2010年12月确诊548例急性IS患者为病例组,993例社区人群为对照组.收集年龄、性别等流行病学信息,测量血压,并检测血糖(GLU)、三酰甘油(TC)、胆固醇(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)和血浆hs-CRP浓度.采用聚合酶链反应(Polymerase chain reaction PCR)-限制性内切酶片段长度多态性(Restriction fragment length polymorphism RFLP)的方法进行基因分型.结果 IS组中血浆hs-CRP水平(3.534±3.484) mg/L及hs-CRP升高(≥3.0 mg/L)比例(43.1％)都显著高于对照组[(1.957±2.344) mg/L,16.6％](t=9.475,P＜0.01;x2=128.326,P ＜0.01).CRP基因rs3093059和rs3091244与IS呈负相关,在校正混杂因素后,rs3093059位点相加模型和显性模型的比值比(OR)及其95％可信区间(95％ CI)分别为0.697 (0.528～0.921)、0.671 (0.487～0.923).rs3091244的显性模型的OR值(95％ CI)为0.728(0.536～0.988).在IS组和对照组,CRP基因rs876537、rs3093059、rs3091244都与血浆hs-CRP浓度升高(≥3.0 mg/L)呈正相关(P＜0.05).结论 CRP基因变异与IS呈负相关而与血浆hs-CRP水平升高呈正相关,而hs-CRP水平升高与IS呈正相关,表明血浆hs-CRP水平升高可能是伴随IS而发生.%Objective To investigate the association of C-reactive protein (CRP) gene polymorphisms and plasma hs-CRP level,and effect on the genetic susceptibility of ischemic stroke (IS).Methods A case-control study was conducted and 548 patients with acute ischemic stroke and 993 agematched controls from community-based population were included in this study.Epidemiological questionnaires were managed to collect for demographic information.Blood pressure was measured and blood glucose,triacylglycerol,cholesterol,and high sensitivity C-reaction protein (hs-CRP) were detected.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping of CRP gene in all participants.Results The levels of plasma hs-CRP and the proportion of elevated plasma hs-CRP (≥3.0 mg/L) in the ischemic stroke patients (3.534 ± 3.484) mg/L (43.1％) were significantly higher than those of controls (1.957 ±2.344) mg/L (16.6％),t =9.475,P ＜ 0.01,x2 =128.326,P ＜ 0.01.The results of association analysis indicated that rs3093059 and rs3091244 of CPR gene presented statistical associations with ischemic stroke.After correction for confounding factors,ORs (95％ CI) of additive model and dominant model of rs3093059 were 0.697 (0.528-0.921),0.671 (0.487-0.923) respectively.ORs 95％ CI) of dominant model of rs3091244 was 0.728 (0.536-0.988).Further analysis indicated the polymorphism of rs876537,rs3093059,rs3091244 of CPR genotyping were significantly associated with plasma hs-CRP elevation (≥ 3.0 mg/L) both in ischemic stroke patients and in controls (P ＜0.05).Conclusion The CRP genetic polymorphisms were negatively associated with ischemic stroke,and positively corrleted with plasma hs-CRP elevation.However,plasma hs-CPP was positively correlated with ischemic stroke.These results suggested that the plasma hs-CRP levels might be accompanied by ischemic stroke.