CTLA4 gene polymorphisms and multiple sclerosis in Northern Ireland

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.