Polymorphic variants of the genes encoding intrleukin-6 and fibrinogen: Risk for ischemic stroke and fibrinogen levels

The occurrence of alleles and genotypes of polymorphic region -174G>C of the gene IL6 (rs1800795) in patients of Russian ethnicity with ischemic stroke (200 cases) and in the control of the same ethnicity similar in sex and age (140 control subjects) has been analyzed. Reliable differences were revealed in the carriage frequency of allele IL6 ^*-174G in homozygous and heterozygous form (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered a risk factor for the development of ischemic stroke, and in the carriage frequencies of protective genotype IL6 ^*-174C/C (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69), respectively. After the patients and the control subjects were divided by gender character, similar differences were observed only between women with ischemic stroke and those from the control group, and after division by age, they were only revealed in groups with members older than 60 years. Complex analysis of the association of ischemic stroke with the carriage of alleles and genotypes of IL6 SNP-174G>C in combination with SNP 4266A>G (Thr312Ala) of the gene FGA (rs6050) and -249C>T of the gene FGB (rs1800788) revealed protective combinations of IL6 ^*-174C/C + FGA ^*4266A and IL6 ^*-174C/C + FGB ^*-249C, which are slightly more reliably associated with ischemic stroke than the one protective genotype IL6 ^*-174C/C and have nearly the same OR value. At the same time, combinations of alternative allele IL6 ^*-174G and the same alleles FGA ^*4266A or FGB ^*-249C were revealed that are characterized by a decrease in both the significance level and the OR value as compared with the carriage of one risk allele IL6 ^*-174G. When there is a combined carriage of the allele IL6 ^*-174G with the genotypes FGA ^*4266A/A, FGB ^*-249C/C or with combinations of these alleles/genotypes, the neutralizing effect is enhanced. In other words, we observed the association of IL6, FGA and FGB allele combinations with ischemic stroke in which IL6 plays the key role and FGA and FGB have a modulating function. In analyzing the association of the alleles/genotypes of three polymorphic regions with the fibrinogen level in plasma, no reliable difference was revealed.