Analysis of Associations of Polymorphisms of Genes Encoding Cytokine Receptors with the Clinical Features of Multiple Sclerosis

Abstract

Objectives. To analyze the associations of gene polymorphisms in the IL7RA (rs689932), IL2RA (rs2104286), and TNFRSF1A (rs1800693) genes with the severity and early clinical characteristics of remitting multiple sclerosis (MS). Materials and methods. Genotyping studies were performed on the polymorphic loci of the IL7RA (rs689932), IL2RA (rs2104286), and TNFRSF1A (rs1800693) genes from 508 ethnically Russian patients with debut of remitting MS followed by analysis of associations of variants of these genes with the severity and variants of MS and the duration of the first remission. Results and conclusions. Assessments on the MSSS identified significant increases in the frequency of the TNFRSF1A*T/T genotype in the group of patients with mild MS (MSSS ≤ 3) and of the TNFRSF1A*C allele in the group of patients with moderate and severe MS (MSSS > 3). Depending on the variant of the manifestations of MS, there was a significant increase in the frequency of the TNFRSF1A*T allele in patients with favorable variants of the manifestations of MS (optical neuritis or sensory impairments), while there was a significant increase in the frequency of the TNFRSF1A*C/C allele in patients with unfavorable variants of manifestations. No associations were found between polymorphisms of the genes of interest with the duration of first remission. Associations between variants of the study genes and the clinical characteristics of MS being compared were also sought in relation to the polymorphic locus of the CTLA4 gene (rs231775), for which an association has previously been established between carriership of the CTLA4*G allele and short-duration first remissions (up to one year). Carriership of the (CTLA4*G + TNFRSF1A*C) combination was more significant than carriership of CTLA4*G alone and was associated with this same characteristic. An additional combination was found, the (CTLA4*G/G + IL7RA*T) combination, which was associated with short first remission. No other differences in carriership frequencies of allele combinations were seen in relation to the clinical characteristics of MS.