title: Investigation of gene-gene interactions between CD40 and CD40L in Polish multiple sclerosis patients.
abstract: CD40-CD40L interaction is necessary for the activation of both humoral and cellular immune response and has been suggested to play a role in the pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined influence of the CD40 and CD40L variants on MS susceptibility and progression on well-defined Polish population. Our investigation revealed that CT individuals in rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC individuals (OR = 1.44; 95%CI = 1.03-2.1; p = 0.032), while this risk for TT individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19-4.78; p = 0.014). Moreover, for the first time, we observed the association of CD40 gene with MS development and progression. We observed that for the rs1883832CC individuals the age at diagnosis was on average 2 years lower than for the rs1883832CT and rs1883832TT individuals (CI95% = -3.69-(-0.29); p = 0.023). Additionally, we detected that individuals with TT and CT genotypes showed lower risk of developing secondary progressive course in comparison to those with CC genotype. For rs1883832TT individuals this risk was 4-fold lower (HR = 0.24; CI95% = 0.10-0.53; p = 0.00062). Despite the fact that CD40-CD40L pathway plays a key role in development of autoimmune diseases, we were not able to detect gene-gene interactions between CD40 and CD40L polymorphisms associated with multiple sclerosis.
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: M
authors.initials: M
authors.lastname: Wagner
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: A
authors.initials: A
authors.lastname: Wisniewski
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Bilinska
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Pokryszko-Dragan
authors.affiliation: Department and Clinic of Neurology, Wroclaw Medical University, ul. Borowska 213, 50-566 Wrocław, Poland.
authors.forename: M
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: P
authors.initials: P
authors.lastname: Kusnierczyk
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: M
authors.initials: M
authors.lastname: Jasek
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D002648:Child; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand
keywords: CD40; CD40L; Gene–gene interactions; Multiple sclerosis