title: CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis.
abstract: The balance between CD28 and CTLA-4 signalling is important for regulation of the immune response. We were interested whether a genetically mediated disturbance of this balance could be related to susceptibility or severity of multiple sclerosis (MS). We examined three polymorphisms in these genes, CTLA-4-318, CTLA-4+49 and CD28-I3+17, in 514 patients with MS and 181 controls. As the loci cannot be assumed independent of each other, we analysed the effects of each of the three polymorphisms corrected for the presence of the other two. We found no association between carriership of any of the alleles either with susceptibility to MS or with clinical features. For a subgroup of patients, longitudinal magnetic resonance imaging (MRI) data were available. We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease.
authors.affiliation: Department of Neurology, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands. T.vanVeen@azvu.nl
authors.forename: Tineke
authors.initials: T
authors.lastname: van Veen
authors.forename: J Bart A
authors.initials: JB
authors.lastname: Crusius
authors.forename: Lisa
authors.initials: L
authors.lastname: van Winsen
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: A
authors.initials: A
authors.lastname: Salvador Peña
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001921:Brain / Q000503:physiopathology; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen; D018450:Disease Progression; D004843:Epistasis, Genetic; D005260:Female; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers