Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
Autoimmun Rev. 2010 Apr;9(6):407-13. doi: 10.1016/j.autrev.2009.11.001. Epub 2009 Nov 5.
To identify HLA-DRB1 alleles contributing to susceptibility to multiple sclerosis (MS) in a Colombian population and to estimate the common effect size of HLA class II on MS susceptibility in Latin American populations through a meta-analysis.
A total of 65 Colombian patients with MS and 184 matched controls were included. HLA-DRB1 typing was done using the sequence-specific oligonucleotide probe method. A bivariate and a multivariate logistic regression analyses were done. Case-control studies performed in Latin America were searched up to January 2009 through a systematic review of the literature. Effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model.
A total of 464 cases and 2581 controls from 7 studies and the results of the present study in Colombians were analyzed. HLA-DRB115 (OR: 2.3; 95% CI: 1.68-3.07; p<0.001) and HLA-DQB106 (OR: 2.2; 95% CI: 1.54-3.07; p<0.001) groups as well as DRB11501 (OR: 2.6; 95% CI: 1.67-4.02; p<0.001), DRB11503 (OR: 2.2; 95% CI: 1.39-3.62; p=0.001) and DQB10602 (OR: 2.5; 95% CI: 1.66-3.71; p<0.001) alleles were found to be risk factors for MS. The myelin basic protein immunodominant sequence (221)VHFFKNIVT(229) was predicted to strongly and simultaneously bind to HLA-DRB11501 and *1503.
The current study highlights the effect size of HLA class II in MS in Latin America and confirms similar allelic risk factors across diverse populations. Receptor-ligand interactions in the HLA-antigenic peptide complex could have potential predictive and therapeutical implications.
在哥伦比亚人群中鉴定与多发性硬化症(MS)易感性相关的 HLA-DRB1 等位基因,并通过荟萃分析估计 HLA Ⅱ类在拉丁美洲人群中对 MS 易感性的常见效应大小。
共纳入 65 例哥伦比亚 MS 患者和 184 例匹配对照。采用序列特异性寡核苷酸探针方法进行 HLA-DRB1 分型。进行了双变量和多变量逻辑回归分析。通过系统文献回顾,检索至 2009 年 1 月拉丁美洲进行的病例对照研究。采用随机效应模型获得效应总结比值比(OR)和 95%置信区间(CI)。
分析了来自 7 项研究的共 464 例病例和 2581 例对照,以及哥伦比亚的本研究结果。HLA-DRB115(OR:2.3;95%CI:1.68-3.07;p<0.001)和 HLA-DQB106(OR:2.2;95%CI:1.54-3.07;p<0.001)组以及 DRB11501(OR:2.6;95%CI:1.67-4.02;p<0.001)、DRB11503(OR:2.2;95%CI:1.39-3.62;p=0.001)和 DQB10602(OR:2.5;95%CI:1.66-3.71;p<0.001)等位基因被发现是 MS 的危险因素。髓鞘碱性蛋白免疫显性序列(221)VHFFKNIVT(229)被预测为同时强烈结合 HLA-DRB11501 和 *1503。
本研究强调了 HLA Ⅱ类在拉丁美洲 MS 中的效应大小,并证实了不同人群中存在相似的等位基因危险因素。HLA-抗原肽复合物中的受体-配体相互作用可能具有潜在的预测和治疗意义。