Genetic Variants in the C-Reactive Protein Gene Are Associated with Microangiopathic Ischemic Stroke
Genetic Variants in the C-Reactive Protein Gene Are Associated with Microangiopathic Ischemic Stroke
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DOI：
10.1159/000319021
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Ringelstein, E. Bernd
中科院分区：
文献类型：
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作者：
Kuhlenbaeumer, Gregor;Huge, Andreas;Ringelstein, E. Bernd
背景和目的：C反应蛋白（CRP）是心血管疾病和缺血性脑卒中的独立危险因素。CRP血清水平受CRP基因遗传变异的影响。研究缺血性中风和CRP基因多态性之间的关系产生了模棱两可的结果。在这里，我们调查单核苷酸多态性（SNPs）在CRP基因在一个大的德国缺血性中风样本。研究方法：在病例对照设计中，对1,669例因大动脉粥样硬化、心源性栓塞或脑微血管病而发生缺血性卒中的患者进行CRP基因中4个单倍型标签SNP（rs3093075、rs 1205、rs 1130864和rs 1800947）的基因分型，这些SNP已被证明会影响CRP血清浓度。从2项前瞻性基于人群的研究（多特蒙德健康研究和波美拉尼亚健康研究）中抽取地理匹配的对照。使用SNP和单倍型方法评估SNP与卒中之间的遗传关联。通过logistic回归对结果进行协变量校正。结果：4个CRP SNPs均位于一个连锁不平衡区。没有一个SNP或SNP单倍型与缺血性卒中整体相关。三个SNPs（rs3093075、rs 1130864和rs 1800947）显示与微血管病性卒中显著相关。一个常见的4-SNP单倍型是保护性的，而2个罕见的单倍型赋予微血管病性中风的易感性。在调整性别、年龄、高血压、糖尿病和高胆固醇血症以及使用“错误发现率”方法校正多重测试后，所有相关性仍然显著。结论：在德国大样本中风中，CRP基因的遗传变异与微血管病性中风相关，而与大血管病性中风或心源性栓塞性中风无关。版权所有（C）2010 S. Karger AG，巴塞尔
Background and Purpose: 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. Methods: 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. Results: 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. Conclusion: Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample. Copyright (C) 2010 S. Karger AG, Basel