C反应蛋白基因多态性与缺血性脑卒中患者血浆高敏C反应蛋白水平的相关性

摘要

目的 研究C反应蛋白(CRP)基因多态性与缺血性脑卒中患者血浆超敏CRP(hs-CRP)水平的相关性. 方法 548例缺血性脑卒中患者,993例健康体检者为对照组.采用PCR-限制性片段长度多态性(PCR-RFLP)法检测CRP基因的单核苷酸多态性(rs876537、rs3093059、rs3091244),同时测定血浆hs-CRP浓度,采用Logistic回归分析CRP基因多态性与血浆hs-CRP水平的关系. 结果 (1)缺血性脑卒中组血浆hs-CRP浓度和hs-CRP浓度增高(≥3.0 mg/L)比例均显著高于健康对照组[(3.5±3.5) mg/L比(2.0±2.3) mg/L,t=10.74,P＜0.05; 43.1％比16.6％,t=23.45,P＜0.05].(2)缺血性脑卒中组比健康对照组具有更高水平的传统的血管危险因素,包括相对较高的血压值[(收缩压(145.3±22.1)比(134.9±19.5) mmHg,t=14.30,P＜0.05;舒张压(88.1±12.7)比(81.4±12.4),t=12.44,P＜0.05)]和低密度脂蛋白胆固醇浓度[(2.7±0.9)比(2.3±0.7),t=9.72,P＜0.05],以及相对较低的高密度脂蛋白胆固醇浓度[(1.2±0.3)比(1.4±0.3),t=-12.89,P＜0.05].(3)CRP基因rs876537和rs3093059与缺血性脑卒中组血浆hs-CRP浓度增高具有显著相关性.校正年龄、性别、高血压、2型糖尿病等因素后的rs3093059的加性模型、显性模型的OR(95％ CI)分别为1.548(1.103～2.171),1.562(1.070～2.281),均P＜0.05.rs876537的加性模型和显性模型在校正其他影响因素后的OR(95％ CI)分别为1.368(1.067～1.753),1.719(1.190～2.482),均P＜0.05. 结论 缺血性脑卒中患者比健康人群具有更高水平的血浆hs-CRP浓度;CRP基因rs876537和rs3093059与缺血性脑卒中患者血浆hs-CRP浓度增高(≥3.0 mg/L)呈显著相关性.%Objective To investigate the association between the polymorphism of C-reactive protein (CRP) gene and plasma level of hs-CRP in patients with ischemic stroke.Methods 548 patients with acute ischemic stroke were considered to be the case group and 993 age-matched healthy controls were randomly selected from community-based population.Three tagging SNPs of the CRP gene (rs876537,rs3093059,and rs3091244) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The plasma hs CRP levels were measured by routine method and multiple logistic regression was applied to evaluate genetic effect on plasma hs-CRP level.Results (1) The hs-CRP concentration and elevation (≥3.0 mg/L) proportion were significantly higher in case group than in control group [(3.534 ± 3.484) mg/L vs.(1.957 ± 2.344) mg/L,43.1％ vs.16.6％,t=10.74 and 23.45,both P＜0.05].(2) Compared with controls,the case group had higher conventional vascular risks,including higher blood pressure [SBP:(145.33 ± 22.11) vs.(134.92±19.48) mmHg,t=14.30,P＜0.05; DBP:(88.14±12.72) vs.(81.42± 12.44) mmHg,t=12.44,P＜0.05],higher low-density lipoprotein cholesterol [(2.714±0.904)vs.(2.286 ± 0.704) mmol/L,t =9.72,P＜ 0.05],and lower concentration of high-density lipoproteincholesterol [(1.213±0.317) vs.(1.438±0.262) /L,t=-12.89,P＜0.05].(3) Both rs876537 and rs3093059 polymorphism of CRP gene showed statistical associations with elevation of plasma hs-CRP level in case group.After adjusted for covariates including age,sex,hypertension,type 2 diabetes and other factors,additive model and dominant model of rs3093059 showed that the adjusted ORs (95 ％ CI) were 1.548 (1.103-2.171),1.562 (1.070-2.281) respectively (both P＜ 0.05).And ORs (95％ CI) of additive model and dominant model of rs876537 were 1.368 (1.067-1.753),1.719 (I.190-2.482) respectively after adjusted for covariates (both P ＜ 0.05).Conclusions Plasma hs-CRP concentration is significantly higher in ischemic stroke patients than in healthy population.The polymorphism of rs876537 and rs3093059 of CRP gene has association with elevation of plasma hs-CRP level in ischemic stroke patients.