[Complex analysis of genetic predisposition to ischemic stroke in Russians]

Abstract

Carriage frequencies of alleles and genotypes of 10 functionally important single nucleotide polymorphisms that are located in genes FGA, FGB, APOE, LPL, ACE and CMA1 were analyzed in the ischemic stroke (IS) patients of Russian ethnic descent and in the control group of the same ethnic descent and of similar gender and age. Comparison between patients and control group revealed no significant differences in frequencies of individual alleles and genotypes for all the polymorphic loci studied. However, complex analysis of genetic predisposition using APSampler algorithm revealed carriage of allele (-491A) APOE as a predisposing factor for IS (p = 0.044, OR 3.8, 95% CI 1.0-15.1). Accordingly, carriage of genotype (-491T/T) APOE was associated with resistance to IS (p = 0.044, OR 0.26, 95% CI 0.07-1.0). The allele -249C FGB carriage addition to this genotype enhances its protective properties, p-value of the combination is 2-fold lower than that of the genotype (-491T/T) APOE (OR 0.17, 95% CI 0.04-0.8). Two more protective combinations were identified: biallelic (-427C) APOE + (1595G) LPL and triallelic (-491C) APOE + (1595G) LPL + (-1903G) CMAI (in both cases p = 0.0052, OR 0.18, 95% CI 0.05-0.66). Overall, involvement in formation of the risk of IS development in Russians was evidenced for alleles of four genes: APOE, FGB, LPL and CMA1, where APOE gene involvement was evidenced for alleles of two polymorphic loci, -491T and -427C. Linkage analysis suggested that involvement of these loci in insusceptibility to IS is mutually independent.