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

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; andALOX5AP: 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.

Automated summary

The PDE4D rs966221 polymorphism is significantly associated with recurrent stroke risk, with GA + GG genotype having 1.399 times the risk. The other five SNPs showed no significant association with recurrent ischemic stroke risk.