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

•SNPs in CD28, CTLA-4, CD80 and CD86 genes may constitute MS risk factors.•Stratification for HLA-DRB1*15:01 may help to reveal MS risk factors.•Gene-gene interactions may influence risk and outcome of MS.

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.

Graphical abstractThe association of rs231775 A > G polymorphism of CTLA-4 with MS susceptibility in HLA-DRB1*15:01(+) and HLA-DRB1*15:01 (−) individualsDownload high-res image (140KB)Download full-size image