Polymorphisms in CD28, CTLA-4, CD80 and CD86 genes may influence the risk of multiple sclerosis and its age of onset

Abstract CD28/CTLA-4–CD80/CD86 molecules play an important role in the regulation of T cells activation. Defects in proteins involved in this pathway may lead to the development of autoimmune diseases in which T cells are involved. In this case–control study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28 , CTLA-4 , CD80 and CD86 genes with susceptibility to MS and/or its progression. We also took into account HLA-DRB1 * 15 : 01 status. Moreover, this study aimed to determine the possible gene-gene interactions between examined SNPs associated with the susceptibility to MS and its outcome. Our investigation revealed that in HLA-DRB1 * 15 : 01 negative individuals, G allele in rs231775A > G of CTLA-4 gene was associated with higher risk of multiple sclerosis. Additionally, the association of rs2715267T > G of CD86 gene with MS susceptibility was detected. In details, carriers of G allele at this polymorphic site possessed higher risk of MS in comparison to TT homozygotes. On the other hand, the lower risk of MS was observed in individuals carrying A allele at the rs1599795T > A polymorphic site of CD80 . Furthermore, the analysis revealed an interaction between three polymorphisms: rs3116496T > C ( CD28 ), rs6641T > G ( CD80 ) and rs17281995G > C ( CD86 ), associated with the age of MS onset.