Association between CPR-related genetic variants and risk of ischemic stroke: a nested case-control study

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.