Association of integrin alpha2 gene variants with ischemic stroke

Abstract

Genetic variants in the gene encoding integrin alpha2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P=0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P=0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes.

Figure 1

Linkage equilibrium blocks in the white (left) and nonwhite (right) patient groups. Numbers within the diamonds are D′ values for the respective SNP pairs. Solid red diamonds represent absolute LD (D′ =1), blue diamonds represent strong LD with low level of significance. Numbers in gray within white diamonds represent a high probability or evidence of historical recombination.