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

Association of the C-reactive protein gene polymorphisms and plasma hs-CRP level in ischemic stroke

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（PolymerasechainreactionPCR）-限制性内切酶片段长度多态性（RestrictionfragmentlengthpolymorphismRFLP）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（≥3．0mg／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．叭）。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、m3093059、rs3091244都与血浆hs—CRP浓度升高（≥3．0mg／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 isehemic stroke （IS）. Methods A case-control study was conducted and 548 patients with acute ischemic stroke and 993 age- matched controls from communlty-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. O1. The results of association analysis indicated that rs3093059 and rs3091244 of CPR gene presented statistical associations with isehemic 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 isehemie stroke patients and in controls （P 〈 0. 05）. Conclusion The CRP genetic polymorphisms were negatively associated with isehemic stroke, and positively eorrleted with plasma hs-CRP elevation. However, plasma hs-CRP was positively correlated with isehemie stroke. These results suggested that the plasma hs-CRP levels might be aeeompanied by ischemic stroke.