A total of 326 patients with multiple sclerosis (MS) according to the McDonald criteria (2005) were recruited to the study. Single nucleotide polymorphisms in the CD40 gene (rs6074022, rs1883832, rs1535045 and rs11086998) and the KIF1B gene (rs10492972 and rs3135388) were genotyped using TaqMan technology. We found a significant association of rs1883832 (risk allele T, OR=1.74, 95% CI 1.34-2.32, p=2.96·10-7) and rs3135388 (risk allele T, OR=3.23, 95% CI 2.43-4.29, p=3.8·10-17) with the risk of MS in the Novosibirsk region population. The study demonstrated a significant effect of genetic factors on phenotypic expression of MS: an C allele of rs6074022 polymorphism (CD40) was associated with a higher rate of MS progression, and the TT genotype of rs1535045 was associated with a slower progression of MS and early MS onset. A more benign course and a higher frequency of an T allele of rs3135388 (44% vs 33%, p=0.003) was found in familial cases compared to sporadic cases. The further specific research is needed for understanding the genetic basis of susceptibility to MS.