Compston Alastair, Sawcer Stephen
University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom.
Curr Neurol Neurosci Rep. 2002 May;2(3):259-66. doi: 10.1007/s11910-002-0085-3.
The increased recurrence risk within families indicates a role for genetic factors in the etiology of multiple sclerosis. Genes may influence susceptibility to the development of multiple sclerosis and the subsequent course of the disease. To date, associations have only been demonstrated consistently with class II major histocompatibility complex (MHC) alleles. The relatively low yield from additional candidate gene studies is only modestly advanced by several whole-genome linkage analyses, and by the first in a series of planned whole-genome linkage disequilibrium screens for allelic associations. The aims of linkage and association are to narrow the search for chromosomal regions encoding genes for multiple sclerosis and, with information from the human gene project, suggest new positional candidates. In time, it is expected that these genes will include some that confer susceptibility to the general process of autoimmunity, others that are specific for multiple sclerosis in all populations, some that act only in defined ethic groups, and those that determine particular phenotypes or shape the clinical course. These genetic analyses are predicated on the assumption that multiple sclerosis is one disease; a major part of future studies will be to resolve the question of disease heterogeneity in multiple sclerosis. When eventually in place, the potential of this genetic knowledge for improved understanding of the pathogenesis of multiple sclerosis and designing novel treatments is considerable.
家族中复发风险的增加表明遗传因素在多发性硬化症的病因中起作用。基因可能影响对多发性硬化症发生的易感性以及疾病的后续病程。迄今为止，仅始终如一地证明了与II类主要组织相容性复合体（MHC）等位基因有关联。额外的候选基因研究的相对低收益仅通过几项全基因组连锁分析以及一系列计划中的用于等位基因关联的全基因组连锁不平衡筛查中的第一项略有进展。连锁和关联分析的目的是缩小对编码多发性硬化症基因的染色体区域的搜索范围，并利用人类基因计划的信息，提出新的定位候选基因。随着时间的推移，预计这些基因将包括一些赋予自身免疫一般过程易感性的基因，其他一些对所有人群中的多发性硬化症具有特异性的基因，一些仅在特定种族群体中起作用的基因，以及那些决定特定表型或塑造临床病程的基因。这些遗传分析基于多发性硬化症是一种疾病的假设；未来研究的一个主要部分将是解决多发性硬化症中疾病异质性的问题。当最终确定后，这种遗传知识对于更好地理解多发性硬化症的发病机制和设计新疗法的潜力是巨大的。
