title: Analysis of the C/T(-1) single nucleotide polymorphism in the CD40 gene in multiple sclerosis.
abstract: The costimulatory CD40-CD40L pathway plays a critical role in the generation and maintenance of adaptive immune responses. Genetic interference of CD40-CD40L interactions strongly influences the onset and course in many autoimmune disease models including experimental autoimmune encephalomyelitis. We analysed the association of a single nucleotide polymorphism of the CD40 gene (C/T(-1)) in 287 patients with multiple sclerosis (MS) and 184 matched controls. No significant differences were found in the frequency of the C/T(-1) polymorphism between the patients with MS and the controls (53% vs 49%) or among different MS subtypes. Cell surface expression of CD40 did not differ within the different genotypes, but carriers of the T allele showed a trend for a lower stimulatory index compared with individuals with the CC genotype. Although these subtle differences indicate functional consequences in the immune stimulatory capabilities related to the CD40 C/T(-1) polymorphism, our population-based study found no association with disease susceptibility or disease course in MS.
authors.affiliation: Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Bayerische Julius-Maximilians Universität, Würzburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Buck
authors.forename: A
authors.initials: A
authors.lastname: Kroner
authors.forename: P
authors.initials: P
authors.lastname: Rieckmann
authors.forename: M
authors.initials: M
authors.lastname: Mäurer
authors.forename: H
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D019013:CD40 Antigens / Q000235:genetics*; D002648:Child; D003597:Cytosine Nucleotides / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D013942:Thymine Nucleotides / Q000235:genetics
chemical_list: D019013:CD40 Antigens; D003597:Cytosine Nucleotides; D013942:Thymine Nucleotides