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

Marta Wagner, Maciej Sobczyński, Lidia Karabon, Małgorzata Bilińska, Anna Pokryszko-Dragan, Edyta Pawlak-Adamska, Małgorzata Cyrul, Piotr Kuśnierczyk, Monika Jasek

Journal of Neuroimmunology, Volume 288, 15 November 2015, Pages 79–86

Highlights
 

  • 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.

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, CD80and 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.


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About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

This online Resource Centre has been made possible by a donation from EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.

Note that EMD Serono, Inc., has no editorial control or influence over the content of this Resource Centre. The Resource Centre and all content therein are subject to an independent editorial review.

The Grant for Multiple Sclerosis Innovation
supports promising translational research projects by academic researchers to improve understanding of multiple sclerosis (MS) for the ultimate benefit of patients.  For full information and application details, please click here

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