Ramagopalan Sreeram V, Knight Julian C, Ebers George C
Wellcome Trust Centre for Human Genetics, UK.
Curr Opin Neurol. 2009 Jun;22(3):219-25. doi: 10.1097/WCO.0b013e32832b5417.
Multiple sclerosis (MS) is the most common neurological disease affecting young adults. The cause is unknown, but detailed epidemiological and genetic studies have shown a clear inherited component. We review here some of the recent findings of MS genetics with a particular focus on genes of the major histocompatibility complex (MHC).
Recent studies add further complexity to the role of the MHC in MS. Reported MHC associations are complex, involving haplotypes rather than single alleles and may involve epigenetic mechanisms and other modulators of gene expression. MHC class II haplotypes display a hierarchy of risks, including protective effects and epistatic interactions, which together dwarf any non-MHC genetic effect. Genes in the MHC region have been shown to influence disease severity, display parent-of-origin effects and interact with a major environmental candidate for MS, vitamin D.
The MHC class II association with MS is not as straightforward as previously thought. A complete understanding of the epistatic interactions and epigenetic features of this region will be important to understand disease pathogenesis and likely aid the discovery of new therapeutics.
多发性硬化症（MS）是影响年轻人的最常见神经系统疾病。其病因不明，但详细的流行病学和遗传学研究已表明存在明显的遗传因素。我们在此回顾MS遗传学的一些最新发现，特别关注主要组织相容性复合体（MHC）的基因。
近期研究使MHC在MS中的作用更加复杂。报道的MHC关联很复杂，涉及单倍型而非单个等位基因，可能涉及表观遗传机制和其他基因表达调节因子。MHC II类单倍型表现出风险等级，包括保护作用和上位性相互作用，这使得任何非MHC遗传效应都显得微不足道。MHC区域的基因已被证明会影响疾病严重程度，表现出亲本来源效应，并与MS的一个主要环境候选因素维生素D相互作用。
MHC II类与MS的关联并不像以前认为的那么简单。全面了解该区域的上位性相互作用和表观遗传特征对于理解疾病发病机制很重要，并且可能有助于发现新的治疗方法。
