Several studies suggest that the histocompatibility complex (HLA) class I region harbours genes modulating multiple sclerosis (MS) susceptibility independently from the effect of class II alleles. A candidate gene in this region is MOG, encoding the myelin oligodendrocyte glycoprotein. A significant association with the missense variation V142L (rs2857766) was previously reported in a small sample of 50 Italian MS patients. We confirmed this result in two independent Italian sample sets consisting of 878 MS patients and 890 matched controls (P=6.6 x 10(-4)) and 246 trio families (P=1.5 x 10(-3)). The comparison of genotype frequencies suggested a dominant-protective effect of L142. In the combined sample sets L142 conferred an odds ratio (OR)=0.70 (95% confidence interval (CI): 0.60-0.82) that remained similar after accounting for HLA-DRB1(*)15 carrier status. The association with MOG V142L was still significant after conditioning for all DRB1 alleles (P=0.035). Eleven additional single nucleotide polymorphisms in the MOG gene (namely -1077T/C, -910T/C, -875A/G, -93T/C, S5S, Indel L22, V145I, +814C/T, +900A/G, +1024A/T, +1059C/T), two microsatellites in the MOG 5' flanking (MOGCA) and 3' untranslated (MOGTAAA) regions and four microsatellites in the HLA-class I region, from HLA-B to HFE, (namely MIB, D6S265, D6S1683 and D6S2239) were tested by transmission disequilibrium test in 199 trio families. None of these polymorphisms or of their haplotypic combinations showed a significant transmission distortion, in the absence of V142L. In conclusion, MOG V142L, or an untested variant in tight-linkage disequilibrium with it, is an independent MS susceptibility-modulating factor in the HLA class I region.

中文翻译：

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在意大利，MOG基因的序列变异与多发性硬化症易感性有关。

几项研究表明，组织相容性复合体（HLA）I类区域包含独立于II类等位基因的作用而调控多发性硬化（MS）敏感性的基因。该区域的候选基因是MOG，其编码髓磷脂少突胶质细胞糖蛋白。先前在50例意大利MS患者的小样本中报告了与错义变异V142L（rs2857766）的显着关联。我们在包括878名MS患者和890名相匹配的对照（P = 6.6 x 10（-4））和246个三重家庭（P = 1.5 x 10（-3））的两个独立的意大利样本集中证实了这一结果。基因型频率的比较表明L142具有显性保护作用。在合并的样本集中，L142的比值比（OR）= 0.70（95％置信区间（CI）：0.60-0）。82）在考虑了HLA-DRB1（*）15的携带者身分后仍然相似。在对所有DRB1等位基因进行调节后，与MOG V142L的关联仍然很显着（P = 0.035）。MOG基因中的其他11个单核苷酸多态性（即-1077T / C，-910T / C，-875A / G，-93T / C，S5S，Indel L22，V145I，+ 814C / T，+ 900A / G，+ 1024A / T，+ 1059C / T），MOG 5'侧翼（MOGCA）和3'非翻译（MOGTAAA）区域中的两个微卫星，以及HLA I类区域中从HLA-B到HFE的四个微卫星（即MIB， D6S265，D6S1683和D6S2239）在199个三人家庭中通过传播不平衡测试进行了测试。在没有V142L的情况下，这些多态性或其单倍型组合都没有显示出明显的传递畸变。总之，MOG V142L或未经测试的紧密连接不平衡变体，