Department of Neurology, School of Medicine, University of California San Francisco, 513 Parnassus Ave., Room S-256, San Francisco, CA 94143-0435, United States.
Curr Opin Genet Dev. 2011 Jun;21(3):317-24. doi: 10.1016/j.gde.2010.12.006. Epub 2011 Jan 17.
For more than 30 years the only genetic factor associated with susceptibility to multiple sclerosis (MS) was the human leukocyte antigen (HLA) region. Recent advancements in genotyping platforms and the development of more effective statistical methods resulted in the identification of 16 more genes by genome-wide association studies (GWAS) in the last three years alone. While the effect of each of these genes is modest compared to that of HLA, this list is expected to grow significantly in the near future, thus defining a complex landscape in which susceptibility may be determined by a combination of allelic variants in different pathways according to ethnic background, disease sub-type, and specific environmental triggers. A considerable overlap of susceptibility genes among multiple autoimmune diseases is becoming evident and integration of these genetic variants with our current knowledge of affected biological pathways will greatly improve our understanding of mechanisms of general autoimmunity and of tissue specificity.
三十多年来，与多发性硬化症（MS）易感性相关的唯一遗传因素是人类白细胞抗原（HLA）区域。近年来，基因分型平台的进步和更有效的统计方法的发展，仅在过去三年就通过全基因组关联研究（GWAS）确定了另外 16 个基因。虽然与 HLA 相比，这些基因的作用都较小，但预计在不久的将来，这个列表将显著增加，从而定义了一个复杂的景观，其中易感性可能由不同途径的等位基因变体组合根据种族背景、疾病亚型和特定的环境触发因素来决定。越来越多的证据表明，多种自身免疫性疾病之间存在易感性基因的重叠，将这些遗传变异与我们目前对受影响的生物学途径的了解相结合，将极大地提高我们对一般自身免疫和组织特异性机制的理解。
