title: 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 NGof CTLA-4 gene was associatedwith higher risk ofmultiple sclerosis. Additionally, the association of rs2715267T NGof CD86 gene withMS susceptibilitywas 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 N A polymorphic site of CD80. Furthermore, the analysis revealed an interaction between three polymorphisms: rs3116496T N C (CD28), rs6641T N G (CD80) and rs17281995G N C (CD86), associated with the age of MS onset.
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, |Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wrocław, Poland. Electronic address: marta_wagner@o2.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Department of Genomics, Faculty of Biotechnology, University of Wrocław, ul. Fryderyka Joliot-Curie 14a, 50-383 Wrocław, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sobczyński
authors.affiliation: Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Karabon
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bilińska
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pokryszko-Dragan
authors.affiliation: Department of Experimental Therapy, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawlak-Adamska
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Cyrul
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, |Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, |Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wrocław, Poland. Electronic address: jasek@iitd.pan.wroc.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Jasek
mesh_terms: D000328:Adult; D017668:Age of Onset; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen
keywords: CD28; CD80; CD86; CTLA-4; Gene-gene interactions; Multiple sclerosis