Olsson Tomas, Hillert Jan
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Curr Opin Neurol. 2008 Jun;21(3):255-60. doi: 10.1097/WCO.0b013e3282fd10cc.
We review the current thinking on the genetic aetiology of multiple sclerosis, new aspects of the influence of genes within the human leucocyte antigen (HLA) complex, how discrete non-HLA genes regulating multiple sclerosis start to be unequivocally demonstrated, and how knowledge from the genetics of experimental models of multiple sclerosis can be used.
Different alleles of the class II molecules display a hierarchy of risks including protective effects in multiple sclerosis. In addition, HLA class I genes are associated with the disease. Experimental multiple sclerosis models are regulated by many genes with small effects, more than about 100. Studies in humans suggest a similar situation. Indeed, the two genes unequivocally established, IL2RA and IL7RA, display a low odds ratio in the order of 1.3. We envisage that many more genes of this kind may be unravelled in the years to come.
There are hierarchies of influences from class II genes. Class I genes regulate disease as well. The unambiguous demonstration of non-HLA genes also suggests that many other genes impacting multiple sclerosis can be deciphered in the years to come. A complete knowledge of the most important of these may pave the way for more selective therapy and gene-environment studies.
我们回顾了目前关于多发性硬化症遗传病因的观点，人类白细胞抗原（HLA）复合体内基因影响的新方面，如何明确证明调节多发性硬化症的离散非HLA基因，以及如何利用多发性硬化症实验模型遗传学的知识。
II类分子的不同等位基因在多发性硬化症中表现出风险等级，包括保护作用。此外，HLA I类基因与该疾病相关。实验性多发性硬化症模型受许多效应较小的基因调控，超过100个。对人类的研究表明情况类似。确实，明确确定的两个基因，IL2RA和IL7RA，显示出约1.3的低比值比。我们设想在未来几年可能会发现更多这类基因。
II类基因存在影响等级。I类基因也调节疾病。非HLA基因的明确证明还表明，未来几年可以解读许多其他影响多发性硬化症的基因。对其中最重要基因的全面了解可能为更具选择性的治疗和基因-环境研究铺平道路。
