The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis.本研究针对多发性硬化（multiple sclerosis）展开，通过分析4个队列中患者与健康对照的基因组DNA，探究人类内源性逆转录病毒（human endogenous retroviruses）在该病发病机制中的作用，重点关注多发性硬化与病毒限制基因（viral restriction genes）附近，或携带一个或多个完整/近乎完整基因的内源性逆转录病毒位点（endogenous retroviral loci）附近的多态性之间的关联。我们发现，TRIM5基因内的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）与疾病发生呈负相关。与之相对，单个逆转录病毒位点HERV-Fc1附近的单核苷酸多态性与疾病存在极显著关联。该关联仅局限于一段不含其他已知基因的狭窄基因组区域内。综上，我们认为HERV-Fc1与TRIM5参与了多发性硬化的病因学（etiology）过程。若该研究结果得到独立验证，将为多发性硬化的治疗开辟全新方向。