C-Reactive Protein Gene Contributes to the Genetic Susceptibility of Hemorrhagic Stroke in Men: a Case-Control Study in Chinese Han Population

High-sensitivity C-reactive protein (hsCRP) is an inflammatory marker for the prediction and prognosis of ischemic stroke but there is an absence of evidence for cerebral hemorrhagic events. The aim of this study is to investigate the effects of elevated plasma hsCRP and CRP genetic variants on hemorrhagic stroke (HS). Two hundred thirty-six inpatients with HS and 993 age-matched controls from a community-based population were included in a case-control study and four tagging single nucleotide polymorphsims (tagSNPs) at CRP were genotyped. The association of hsCRP elevation and CRP variants with HS was evaluated by multiple logistic regression. HS cases had a higher median (interquartile) of hsCRP with 5.40 (1.30-10.7) mg/L and a proportion of hsCRP elevation (>= 3 mg/L, 63.4%) than controls [1.20 (0.80-2.20) mg/L, 16.6%], respectively (P < 0.05 for all). No significant difference of genotype or allele frequency of the four SNPs was observed between HS patients and controls (P > 0.05). Further stratified analysis by gender showed that the variants of rs3093059 (T/C) and rs3091244 (C/T/A) were significantly associated with the decreased risk of HS in men and odds ratios (ORs) and 95% confidence intervals (95% CIs) for additive models were 0.515 (0.294-0.903) and 0.578 (0.349-0.96), respectively, after adjusting for covariates. In HS patients, rs3091244 was positively associated with the hsCRP elevation and rs2794521 was negatively associated with hsCRP elevation (P < 0.05). Our findings suggest that hsCRP elevation is associated with the risk of HS and CRP contributes genetic susceptibility to HS in men as well as hsCRP elevation in HS.