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.