A genetic predisposition due to the polygenic system responsible for the formation of immune response plays a key role in the development of multiple sclerosis. We genotyped the following polymorphisms: TNFα (rs1800629), TNFRSF1A (rs4149584), CD40 (rs6074022 and rs11086998) using TaqMan technology. The significant genotype effect on the disability index on EDSS and rate of MS progression was found. The association between GA and AA TNFα genotypes and higher average annual frequency of exacerbations was revealed. Genotypes CC (rs6074022) and GG (rs11086998) were associated with the higher disability level. Genotype CC (rs11086998) was associated with the higher rate of MS progression. The results may be used as potential predictors of high rate of MS progression and allow to tailor treatment on early stages of the disease.