Association between kinase insert domain-containing receptor gene polymorphism and haplotypes and ischemic stroke

Abstract

Kinase insert domain-containing receptor (KDR), a type 2 vascular endothelial growth factor receptor, plays a crucial role in angiogenesis and vascular integrity of blood vessels. We evaluated whether single nucleotide polymorphisms (SNPs) and haplotype of kinase insert domain-containing receptor (KDR) are associated with increased risk of ischemic stroke in the Korean population. Totals of 501 patients with ischemic stroke and 478 controls were screened for the KDR -604T>C, +1192G>A, and +1719A>T SNPs. Subgroup analysis was performed to determine whether the effect of KDR polymorphism is specific to certain etiological subtypes of ischemic stroke. In addition, haplotype frequencies of these three SNPs were analyzed in stroke patients and controls. The SNP +1719T allele was associated with risk of ischemic stroke in a dose-dependent manner (TT vs. AA: adjusted OR: 1.90, 95% CIs: 1.29-2.81, p=0.001 and false discovery rate (FDR)=0.003). Subgroup analysis showed that the SNP +1719T allele had a slight but significant association with small vessel disease type (TT vs. AA: adjusted OR: 1.91, 95% CIs: 1.11-3.29, p=0.02). There was no association between SNP -604 and SNP +1192 and ischemic stroke risk. In haplotype analysis, the T-G-T (-604/+1192/+1719), T-A-T, and C-G-T haplotypes increased the relative risk of ischemic stroke. The KDR +1719A>T polymorphism and its haplotypes are possible genetic determinants for the risk of ischemic stroke.