Association of GWAS-susceptibility loci with ischemic stroke recurrence in a Han Chinese population

J Gene Med. 2021 Jan;23(1):e3264. doi: 10.1002/jgm.3264. Epub 2020 Sep 9.

Abstract

Background: Recently, genome-wide association studies (GWAS) have found many new susceptible genetic variants for ischemic stroke (IS) occurrence. However,the roles of GWAS-susceptibility loci in stroke prognosis are just beginning. The present study aimed to examine whether these GWAS-linked loci polymorphisms are associated with ischemic stroke recurrence in a Chinese population.

Methods: We genotyped six single nucleotide polymorphisms (SNPs) (9p21: rs2383207 and rs4977574; 12p13: rs12425791 and rs11833579; PDE4D: rs966221; and ALOX5AP: rs1050391) in four GWAS-reported ischemic stroke risk genes in 657 patients.

Results: The risk of recurrent stroke was significantly associated with PDE4D rs966221 in the dominant model (p = 0.027)and recessive model (p = 0.027). Furthermore, Kaplan-Meier analyses indicated no significant difference in the rate of recurrent stroke among the three genotypes of other five SNPs. Cox regression analysis showed that the GA + GG genotype within the rs966221 polymorphism had a 1.399-fold risk for stoke recurrence (95% confidence interval = 1.038-1.886; p = 0.027). Stratified analysis revealed that the increased recurrence risk of PDE4D rs966221 was more prominent in the large artery atherosclerosis (LAA) subgroup.

Conclusions: The reults of the present study demonstrate that PDE4D rs966221 may be a valuable biomarker for predicting the recurrent risks of patient with the LAA-IS and adds to our knowledge of the genetic basis of recurrent stroke risk.

Keywords: GWAS-susceptibility loci; ischemic stroke; polymorphism;recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • China / epidemiology
  • Comorbidity
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / epidemiology*
  • Ischemic Stroke / etiology*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Population Surveillance*
  • Proportional Hazards Models
  • Recurrence