Sawcer S, Jones H B, Feakes R, Gray J, Smaldon N, Chataway J, Robertson N, Clayton D, Goodfellow P N, Compston A
University of Cambridge Neurology unit, Addenbrooke's Hospital, UK.
Nat Genet. 1996 Aug;13(4):464-8. doi: 10.1038/ng0896-464.
The population prevalence of multiple sclerosis is 0.1%; however, the risk of the disease in the siblings of affected individuals is very much higher at 3-5%. The importance of genetic factors in accounting for this increased risk is confirmed by the results of twin and adoption studies. Despite the evidence for a strong genetic effect, a weak major histocompatibility complex (MHC) association is the only consistently observed feature in the genetics of multiple sclerosis. Other candidates have been proposed, including genes encoding the immunoglobulin heavy chain, T cell receptor beta chain and APOC2, but none has yet been confirmed. Evidence for linkage and association to the myelin basic protein gene has been reported in a genetically isolated Finnish population, but it has not been possible to reproduce these results in other populations. We used a two-stage approach to search the human genome for the genes causing susceptibility to multiple sclerosis. Two principal regions of linkage are identified, chromosomes 17q22 and 6p21 (MHC). Our results are compatible with genetic models involving epistatic interaction between these and several additional genes.
多发性硬化症的人群患病率为0.1%；然而，患病个体的兄弟姐妹患该病的风险要高得多，为3%-5%。双胞胎和收养研究的结果证实了遗传因素在解释这种风险增加方面的重要性。尽管有证据表明存在强大的遗传效应，但主要组织相容性复合体（MHC）的弱关联是多发性硬化症遗传学中唯一一直观察到的特征。已经提出了其他候选基因，包括编码免疫球蛋白重链、T细胞受体β链和载脂蛋白C2的基因，但尚未得到证实。在一个遗传隔离的芬兰人群中报告了与髓鞘碱性蛋白基因连锁和关联的证据，但无法在其他人群中重现这些结果。我们采用两阶段方法在人类基因组中搜索导致多发性硬化症易感性的基因。确定了两个主要连锁区域，即17号染色体q22和6号染色体p21（MHC）。我们的结果与涉及这些基因和其他几个基因之间上位性相互作用的遗传模型一致。
