Department of Neurology, Leibniz Institute for Atherosclerosis Research, University of Muenster, Muenster, Germany.
Cerebrovasc Dis. 2010;30(5):476-82. doi: 10.1159/000319021. Epub 2010 Aug 24.
C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and ischemic stroke. CRP serum levels are influenced by genetic variation in the CRP gene. Studies investigating the relationship between ischemic stroke and polymorphisms in the CRP gene produced equivocal results. Here we investigate single-nucleotide polymorphisms (SNPs) in the CRP gene in a large German ischemic stroke sample.
In a case-control design, 1,669 patients with ischemic stroke due to large-artery atherosclerosis, cardioembolism or cerebral microangiopathy were genotyped for 4 haplotype tagging SNPs (rs3093075, rs1205, rs1130864 and rs1800947) in the CRP gene which have been shown to influence CRP serum concentrations. Geographically matched controls were drawn from 2 prospective population-based studies, the Dortmund Health Study and the Study of Health in Pomerania. The genetic association between the SNPs and stroke was assessed using SNP and haplotype approaches. Results were adjusted for covariates by logistic regression.
All 4 CRP SNPs reside in one linkage disequilibrium block. None of the SNPs or SNP haplotypes were associated with ischemic stroke as a whole. Three SNPs (rs3093075, rs1130864 and rs1800947) showed a significant association with microangiopathic stroke. A common 4-SNP haplotype was protective while 2 rarer haplotypes conferred susceptibility to microangiopathic stroke. All associations remained significant after adjustment for sex, age, hypertension, diabetes mellitus and hypercholesterolemia and after correction for multiple testing using the 'false discovery rate' method.
Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample.
C 反应蛋白（CRP）是心血管疾病和缺血性卒中的独立危险因素。CRP 血清水平受 CRP 基因的遗传变异影响。研究 CRP 基因多态性与缺血性卒中之间关系的结果存在争议。本研究在一个大型德国缺血性卒中样本中调查 CRP 基因的单核苷酸多态性（SNP）。
采用病例对照设计，对大动脉粥样硬化、心源性栓塞或脑微血管病变所致的 1669 例缺血性卒中患者进行 CRP 基因 4 个单体型标签 SNP（rs3093075、rs1205、rs1130864 和 rs1800947）的基因分型，这些 SNP 已被证明影响 CRP 血清浓度。从两个前瞻性基于人群的研究，即多特蒙德健康研究和波美拉尼亚健康研究中抽取地理位置匹配的对照。采用 SNP 和单体型分析评估 SNP 与卒中的遗传关联。结果通过 logistic 回归调整协变量。
所有 4 个 CRP SNP 均位于一个连锁不平衡块中。没有 SNP 或 SNP 单体型与缺血性卒中整体相关。3 个 SNP（rs3093075、rs1130864 和 rs1800947）与微血管性卒中显著相关。常见的 4-SNP 单体型具有保护作用，而 2 个罕见的单体型易导致微血管性卒中。校正性别、年龄、高血压、糖尿病和高胆固醇血症后，所有关联仍然显著，并且使用“假发现率”方法校正多重检验后仍然显著。
在一个大型德国卒中样本中，CRP 基因的遗传变异与微血管性卒中相关，而与大动脉性或心源性卒中无关。
