Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.

中文翻译：

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CPR相关遗传变异与缺血性中风风险之间的关联：一项嵌套的病例对照研究。

背景：据报道，血清C反应蛋白（CRP）与包括缺血性中风在内的缺血性血管疾病的风险有关。全基因组关联研究揭示了几种与CRP浓度有关的基因变异。方法：我们在一个嵌套病例对照研究中对138例缺血性中风病例和276例对照进行了调查，研究了与缺血性中风相关的CRP相关基因的遗传变异。我们对六个CPR相关基因的整个编码区进行了测序，并选择了合格的SNP。通过多变量条件logistic回归计算了三种遗传模型（加性，显性和隐性），以估计SNP与缺血性卒中风险之间的关联。我们还使用交叉分析计算了基因与环境的相互作用。结果：十分之三的合格SNPs被证明与缺血性中风的风险有关。CRP基因中的rs1800947（添加模型：OR = 2.08，95％CI：1.00-4.23）和HNF1A基因中的rs1169288（添加模型：OR = 1.45，95％CI：1.03-2.06）与缺血性中风的风险增加相关。APOE基因中的rs440446（添加模型：OR = 0.63，95％CI：0.44-0.88）与缺血性中风的风险降低相关。包括SC-GRS和OR-GRS在内的遗传风险评分模型均显示出与缺血性中风的风险显着相关。这三个SNP与吸烟和红肉摄入相互作用。结论：我们的研究表明CRP相关基因的遗传变异与缺血性中风的风险有关。我们的发现可以为缺血性中风的病因提供有用的数据。HNF1A基因（添加模型：OR = 1.45，95％CI：1.03-2.06）中的95％CI：1.00-4.23）和rs1169288与缺血性中风的风险增加相关。APOE基因中的rs440446（添加模型：OR = 0.63，95％CI：0.44-0.88）与缺血性中风的风险降低相关。包括SC-GRS和OR-GRS在内的遗传风险评分模型均显示出与缺血性中风的风险显着相关。这三个SNP与吸烟和红肉摄入相互作用。结论：我们的研究表明CRP相关基因的遗传变异与缺血性中风的风险有关。我们的发现可以为缺血性中风的病因提供有用的数据。HNF1A基因（添加模型：OR = 1.45，95％CI：1.03-2.06）中的95％CI：1.00-4.23）和rs1169288与缺血性中风的风险增加相关。APOE基因中的rs440446（添加模型：OR = 0.63，95％CI：0.44-0.88）与缺血性中风的风险降低相关。包括SC-GRS和OR-GRS在内的遗传风险评分模型均显示出与缺血性中风的风险显着相关。这三个SNP与吸烟和红肉摄入相互作用。结论：我们的研究表明CRP相关基因的遗传变异与缺血性中风的风险有关。我们的发现可以为缺血性中风的病因提供有用的数据。0.44-0.88）与缺血性中风的风险降低相关。包括SC-GRS和OR-GRS在内的遗传风险评分模型均显示出与缺血性中风的风险显着相关。这三个SNP与吸烟和红肉摄入相互作用。结论：我们的研究表明CRP相关基因的遗传变异与缺血性中风的风险有关。我们的发现可以为缺血性中风的病因提供有用的数据。0.44-0.88）与缺血性中风的风险降低相关。包括SC-GRS和OR-GRS在内的遗传风险评分模型均显示出与缺血性中风的风险显着相关。这三个SNP与吸烟和红肉摄入相互作用。结论：我们的研究表明CRP相关基因的遗传变异与缺血性中风的风险有关。我们的发现可以为缺血性中风的病因提供有用的数据。