Department of Neurology, Pudong district Nanhui Central hospital, 2800 Gongwei Road, Shanghai 201300, China.
Autoimmun Rev. 2011 Jun;10(8):474-81. doi: 10.1016/j.autrev.2011.03.003. Epub 2011 Apr 2.
To identify the contribution of HLA-DRB1 alleles to susceptibility or resistance to multiple sclerosis (MS) in Caucasians through a meta-analysis of non-family-based studies.
A systematic review of case-control studies in Caucasians was performed. Studies examining allele or phenotype frequencies were analyzed separately. Odds ratio (OR) and 95% confidence intervals (CIs) were used. We also used the relatively predispositional effect (RPE) method to analyze several allele frequency studies to avoid skewed results due to some strongly associated alleles.
A total of 5464 cases and 7809 controls from 14 allele frequency studies and a total of 5401 cases and 7538 controls from 23 phenotype frequency studies were analyzed. DRB115 was definitely the strongest risk factor for MS (allele group, Pc<0.00013, OR 2.59, 95%CI 2.34-2.87; phenotype group, Pc<0.00013, OR 3.35, 95%CI 2.95-3.80). DRB103 frequencies were significantly increased among MS cases in the phenotype group (Pc= 0.0013, OR 1.21, 95%CI 1.09-1.33) but not in the allele group. DRB114 and DRB107 showed protective effects against MS in both groups (DRB114, allele group, Pc<0.00013, OR 0.53, 95%CI 0.42-0.66; phenotype group, Pc<0.00013, OR 0.57, 95%CI 0.45-0.71; DRB107, allele group, Pc<0.0026, OR 0.75, 95%CI 0.64-0.87; phenotype group, Pc<0.00013, OR 0.67, 95%CI 0.61-0.73). By RPE method, DRB114, and DRB107 showed protective effects after excluding DRB115 from the analysis. DRB103 was significantly higher in MS cases than controls after removing both DRB115 and DRB114.
In Caucasians, we highlighted the definite protective role of HLA-DRB114 and DRB107 for MS. DRB103 is probably the only risk factor for MS besides DRB115 and a common genetic foundation for autoimmune disease. Targeting to these alleles may have potential values in prevention or therapy for MS in the specific population.
通过对非家族性研究的荟萃分析，确定 HLA-DRB1 等位基因对白人多发性硬化症易感性或抗性的贡献。
对白人病例对照研究进行系统评价。分别分析研究等位基因或表型频率的研究。使用比值比（OR）和 95%置信区间（CI）。我们还使用相对倾向性效应（RPE）方法来分析几个等位基因频率研究，以避免由于某些强关联等位基因而导致的偏倚结果。
共分析了 14 个等位基因频率研究的 5464 例病例和 7809 例对照，以及 23 个表型频率研究的 5401 例病例和 7538 例对照。DRB115 肯定是 MS 的最强危险因素（等位基因组，Pc<0.00013，OR 2.59，95%CI 2.34-2.87；表型组，Pc<0.00013，OR 3.35，95%CI 2.95-3.80）。在表型组中，MS 病例中 DRB103 的频率明显升高（Pc=0.0013，OR 1.21，95%CI 1.09-1.33），但在等位基因组中则不然。DRB114 和 DRB107 在两组中均显示出对 MS 的保护作用（DRB114，等位基因组，Pc<0.00013，OR 0.53，95%CI 0.42-0.66；表型组，Pc<0.00013，OR 0.57，95%CI 0.45-0.71；DRB107，等位基因组，Pc<0.0026，OR 0.75，95%CI 0.64-0.87；表型组，Pc<0.00013，OR 0.67，95%CI 0.61-0.73）。通过 RPE 方法，在排除 DRB115 后，DRB114 和 DRB107 显示出保护作用。排除 DRB115 和 DRB114 后，MS 病例中 DRB103 的频率明显高于对照组。
在白种人中，我们强调了 HLA-DRB114 和 DRB107 对 MS 的明确保护作用。DRB103 可能是除 DRB115 之外唯一的 MS 危险因素，也是自身免疫性疾病的共同遗传基础。针对这些等位基因可能在特定人群的 MS 预防或治疗方面具有潜在价值。
