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.

The frequencies of alleles and genotypes for ten functionally significant single-nucleotide polymorphisms were determined in the FGA, FGB, APOE, LPL, ACE , and CMA1 genes for Russian ischemic stroke (IS) patients and for a control group of Russians similar in gender and age distribution. The groups showed no significant differences in the frequencies of individual alleles or genotypes for any polymorphism studied. However, complex analysis of genetic susceptibility by the APSampler algorithm demonstrated that carriership of the APOE (−491A) allele predisposed to IS ( p = 0.044, OR 3.8, 95% CI 1.0–15.1). Correspondingly, the APOE (−491T/T) genotype was associated with resistance to IS ( p = 0.044, OR 0.26, 95% CI 0.07–1.0). The carriership of FGB (−249C) allele together with this genotype enhanced its protective potential, reducing the p value of the combination twofold (OR 0.17, 95% CI 0.04–0.8). Two more protective combinations were identified: biallelic APOE (−427C) + LPL (1595G) and triallelic APOE (−491C) + LPL (1595G) + CMA1 (−1903G). In both cases, p = 0.0052, OR 0.18, and 95% CI 0.05–0.66. Altogether, involvement in the formation of IS risk in Russians was evidenced for alleles of four genes: APOE, FGB, LPL , and CMA1 ; the APOE involvement was demonstrated for alleles of two polymorphic loci: −491T and −427C. Linkage analysis suggested that these loci were involved in IS resistance independently of each other.

For the first time an analysis of contribution of alleles of haemostasis genes, encoding fibrinogen alpha (FGA), fibrinogen beta (FGB) and tissue plasminogen activator (TPA), in genetic susceptibility to and clinical aspects of hemorrhagic stroke (HS) was performed in ethnic Yakuts. HS patients compared to controls demonstrated significant increase of frequency of FGA4266A/A genotype carriage: 26,9% vs 16,1% (p=0,04, OR=1,9, CI 1,0 - 3,8) and corresponding decrease of FGA4266G allele carriage: 73,1% vs 83,9% (p=0,04, OR =0,5, CI 0,3 - 1,0). We identified tri-allelic combination: FGB-249C; FGA4266G; TPA-7351C, which carriage is significantly differed in HS patients with different types of haemorrhage.

Проведен анализ частот встречаемости аллелей и генотипов 10 функционально значимых однонуклеотидных полиморфизмов в генах FGA, FGB, APOE, LPL, ACE и CMA1 в группе русских больных ишемическим инсультом и в контрольной группе лиц той же этнической принадлежности, сходной по полу и возрасту. Не обнаружено значимых различий в частотах отдельных аллелей и генотипов всех рассматриваемых полиморфных участков при сравнении группы больных и контрольной группы. Однако комплексный анализ генетической предрасположенности с использованием алгоритма APSampler показал, что носительство аллеля (–491A) APOE является фактором предрасположенности к ишемическому инсульту (р = 0.044, OШ 3.8, 95% ДИ 1.0–15.1). Соответственно, носительство генотипа (–491Т/T) APOE связано с устойчивостью к ишемическому инсульту (р = 0.044, ОШ 0.26, 95% ДИ 0.07–1.0). Добавление носительства аллеля –249C FGB к этому генотипу улучшает протективные свойства сочетания, снижая значение р в 2 раза (ОШ 0.17, 95% ДИ 0.04–0.8). Найдены еще два протективных сочетания: биаллельное (–427C) APOE + (1595G) LPL и триаллельное (–491C) APOE + (1595G) LPL + + (–1903G) CMA1 (в обоих случаях р = 0.0052, OШ 0.18, 95% ДИ 0.05–0.66). В целом, в формирование риска развития ишемического инсульта у русских вовлечены четыре гена – APOE, FGB, LPL и CMA1, причем у гена APOE – аллели двух полиморфных участков –491T и –427C. Результаты анализа сцепления позволяют предполагать, что эти участки вносят вклад в невосприимчивость к ишемическому инсульту независимо друг от друга.

We examined an association of the C-148T beta-fibrinogen gene polymorphism with fibrinogen level and platelet aggregation in patients with ischemic stroke and in people with vascular risk factors but no ischemic stroke. Among stroke patients, carriers of an -148T allele had significantly higher plasma fibrinogen level and platelet aggregation to norepinephrin compared to the C/C homozygotes. No significant differences in frequencies of a C-148 allele between stroke patients and controls were observed.