Heggarty Shirley, Suppiah Vijayaprakash, Silversides Jonathan, O'doherty Catherine, Droogan Aidan, McDonnell Gavin, Hawkins Stanley, Graham Colin, Vandenbroeck Koen
Applied Genomics Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK.
J Neuroimmunol. 2007 Jul;187(1-2):187-91. doi: 10.1016/j.jneuroim.2007.04.017. Epub 2007 May 23.
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.
在北爱尔兰复发缓解型（RR）和原发进展型（PP）多发性硬化症（MS）患者群体中，对4种细胞毒性T淋巴细胞相关抗原4（CTLA4）基因多态性进行了研究。在246例复发缓解型多发性硬化症（RRMS）患者、84例原发进展型多发性硬化症（PPMS）患者和158名健康对照中，分析了CTLA4启动子（-318 C/T）、第1外显子（+49 A/G）和基因间CT60单核苷酸多态性（SNP），以及在3'非翻译区发现的一个微卫星（AT(n)）。第1外显子+49 A/G SNP的A等位基因（比值比[OR]=1.36；95%置信区间[CI]=1.11 - 1.81；P=0.038），尤其是AA基因型（OR=1.70；95% CI=1.11 - 2.60；P=0.015）与RRMS相关，但与PPMS无关。在PPMS患者群体中，AT(n)微卫星的总体等位基因分布与健康对照有显著差异。在这两种疾病队列中，均未发现与启动子（-318 C/T）或基因间CT60 SNPs有关联。与最近的几项研究一致，我们检测到PPMS患者与RRMS患者相比，+49 G等位基因携带率有升高趋势（66.7%对58.9%），尽管这并不显著。我们的数据突出了CTLA4 +49 A/G和3'非翻译区多态性作为MS疾病进程潜在调节因子的作用。
