Oksenberg J R, Barcellos L F
Department of Neurology, School of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA.
Genes Immun. 2005 Aug;6(5):375-87. doi: 10.1038/sj.gene.6364237.
Compelling epidemiologic and molecular data indicate that genes play a primary role in determining who is at risk for developing multiple sclerosis (MS), how the disease progresses, and how someone responds to therapy. The genetic component of MS etiology is believed to result from the action of allelic variants in several genes. Their incomplete penetrance and moderate individual effect probably reflects epistatic interactions, post-transcriptional regulatory mechanisms, and significant environmental influences. Equally significant, it is also likely that locus heterogeneity exists, whereby specific genes influence susceptibility and pathogenesis in some individuals but not in others. With the aid of novel analytical algorithms, the combined study of genomic, transcriptional, proteomic, and phenotypic information in well-controlled study groups will define a useful conceptual model of pathogenesis and a framework for understanding the mechanisms of action of existing therapies for this disorder, as well as the rationale for novel curative strategies.
令人信服的流行病学和分子数据表明，基因在决定谁有患多发性硬化症（MS）的风险、疾病如何进展以及个体对治疗的反应方面起着主要作用。MS病因的遗传成分被认为是由几个基因中的等位基因变异作用所致。它们的不完全外显率和适度的个体效应可能反映了上位性相互作用、转录后调控机制以及重大的环境影响。同样重要的是，也可能存在基因座异质性，即特定基因在某些个体中影响易感性和发病机制，而在其他个体中则不然。借助新颖的分析算法，在严格控制的研究组中对基因组、转录组、蛋白质组和表型信息进行联合研究，将定义一个有用的发病机制概念模型以及一个框架，用于理解该疾病现有疗法的作用机制以及新的治愈策略的原理。
