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

• Published in: Journal of neuroimmunology Vol. 288; pp. 79 - 86
• Main Authors: Wagner, Marta, Sobczyński, Maciej, Karabon, Lidia, Bilińska, Małgorzata, Pokryszko-Dragan, Anna, Pawlak-Adamska, Edyta, Cyrul, Małgorzata, Kuśnierczyk, Piotr, Jasek, Monika
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2015
• Subjects: Adult; Age of Onset; Allergy and Immunology; B7-1 Antigen - genetics; B7-2 Antigen - genetics; Case-Control Studies; CD28; CD28 Antigens - genetics; CD80; CD86; CTLA-4; CTLA-4 Antigen - genetics; Female; Gene-gene interactions; Genetic Predisposition to Disease - genetics; Genotype; Humans; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - genetics; Neurology; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Risk Factors; CD86; CD28; Multiple sclerosis; CTLA-4; CD80; Gene-gene interactions
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2015.09.004

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.