title: CTLA4 gene polymorphisms and multiple sclerosis in Northern Ireland.
abstract: Four CTLA4 polymorphisms were investigated in a Northern Irish collection of relapsing-remitting (RR) and primary-progressive (PP) multiple sclerosis (MS) patients. The CTLA4 promoter (-318 C/T), exon 1 (+49 A/G) and intergenic CT60 SNPs, as well as a microsatellite found in the 3' UTR (AT(n)) were analysed in 246 RRMS, 84 PPMS and 158 healthy controls. The A allele of the exon 1 +49 A/G SNP (OR=1.36; 95% CI=1.11-1.81; P=0.038), and more so the AA genotype (OR=1.70; 95% CI=1.11-2.60; P=0.015) were associated with RR, but not PPMS. In the PPMS population, overall allele distribution of the AT(n) microsatellite was significantly different from that in the healthy controls. We did not find any association with the promoter (-318 C/T) or intergenic CT60 SNPs in either of the disease cohorts. In concordance with several recent studies, we detected a trend toward higher carriage rates of the +49 G allele in PP vs RR MS patients (66.7% vs 58.9%), though this was not significant. Our data highlight the CTLA4 +49 A/G and 3'UTR polymorphisms as potential modifiers of disease course in MS.
authors.affiliation: Applied Genomics Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Shirley
authors.initials: S
authors.lastname: Heggarty
authors.forename: Vijayaprakash
authors.initials: V
authors.lastname: Suppiah
authors.forename: Jonathan
authors.initials: J
authors.lastname: Silversides
authors.forename: Catherine
authors.initials: C
authors.lastname: O'doherty
authors.forename: Aidan
authors.initials: A
authors.lastname: Droogan
authors.forename: Gavin
authors.initials: G
authors.lastname: McDonnell
authors.forename: Stanley
authors.initials: S
authors.lastname: Hawkins
authors.forename: Colin
authors.initials: C
authors.lastname: Graham
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016001:Confidence Intervals; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D018895:Microsatellite Repeats / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human