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

Yao Zhua*, Shu-Chang Hua*, Pei-Wen Zhenga, Ming-Juan Jina, Meng-Ling Tanga, Kun Chen*ab & Jian-Bing Wang*aa Department of Epidemiology and Biostatistics, School of Public health, Zhejiang University, Hangzhou, Chinab Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaYao Zhu, Master Candidate, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.Shu-Chang Hu, Master degree, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.Pei-Wen Zheng, Master degree, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.Ming-Juan Jin, Ph.D., MD, Associate Professor, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.Meng-Ling Tang, Ph.D., Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.Kun Chen, Ph.D., MD, Professor, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China; Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.Jian-Bing Wang, Ph.D., MD, Associate Professor, Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China.CONTACT Kun Chen ck@zju.edu.cnJian-Bing Wang wangjianbing@zju.edu.cn Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou Zhejiang 310058, China* These authors contributed equally to this work.ABSTRACTBackground: 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.