GWAS-Supported CRP Gene Polymorphisms and Functional Outcome of Large Artery Atherosclerotic Stroke in Han Chinese

Neuromolecular Med. 2018 Jun;20(2):225-232. doi: 10.1007/s12017-018-8485-y. Epub 2018 Mar 19.

Abstract

Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3 months after the index stroke was assessed by the modified Rankin scale. Associations between genotypes and functional outcome of LAA IS were analyzed with logistic regression model. A total of 690 eligible patients (507 males) were evaluated. SNPs rs11265260 (multivariate-adjusted, p = 0.022), rs2794520 (multivariate-adjusted, p = 0.036) and rs3093059 (multivariate-adjusted, p = 0.027) were significantly associated with elevated CRP in acute IS. Two SNPs, rs3093059 (dominant model: adjusted OR 2.49; 95% CI 1.55-4.00; recessive model: adjusted OR 3.67; 95% CI 1.22-11.03) and rs11265260 (dominant model: adjusted OR 2.51; 95% CI 1.56-4.02; recessive model: adjusted OR 4.70; 95% CI 1.63-13.56) independently predicted 3-month poor outcome of first-ever LAA IS, after adjusting for covariates. In addition, haplotype analysis indicated that haplotype GCTGC (adjusted OR 1.76; 95% CI 1.05-2.95; p = 0.031) increased the poor outcome risk. SNPs rs3093059 and rs11265260 in CRP gene may influence the 3-month functional outcome of first-ever LAA IS in Han Chinese.

Keywords: C-reactive protein; Gene; Large artery atherosclerotic stroke; Polymorphism; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Atherosclerosis / complications*
  • Atherosclerosis / genetics
  • C-Reactive Protein / genetics*
  • Comorbidity
  • Ethnicity / genetics*
  • Female
  • Follow-Up Studies
  • Genes, Dominant
  • Genes, Recessive
  • Genome-Wide Association Study*
  • Haplotypes / genetics
  • Humans
  • Male
  • Metabolic Syndrome / epidemiology
  • Middle Aged
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Severity of Illness Index
  • Single-Blind Method
  • Smoking / epidemiology
  • Stroke / ethnology
  • Stroke / genetics*
  • Treatment Outcome

Substances

  • C-Reactive Protein