Jokubaitis Vilija G, Zhou Yuan, Butzkueven Helmut, Taylor Bruce V
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
Curr Treat Options Neurol. 2018 Apr 24;20(6):18. doi: 10.1007/s11940-018-0505-6.
This review will examine the current evidence that genetic and/or epigenetic variation may influence the multiple sclerosis (MS) clinical course, phenotype, and measures of MS severity including disability progression and relapse rate.
There is little evidence that MS clinical phenotype is under significant genetic control. There is increasing evidence that there may be genetic determinants of the rate of disability progression. However, studies that can analyse disability progression and take into account all the confounding variables such as treatment, clinical characteristics, and environmental factors are by necessity longitudinal, relatively small, and generally of short duration, and thus do not lend themselves to the assessment of hundreds of thousands of genetic variables obtained from GWAS. Despite this, there is recent evidence to support the association of genetic loci with relapse rate. Recent progress suggests that genetic variations could be associated with disease severity, but not MS clinical phenotype, but these findings are not definitive and await replication. Pooling of study results, application of other genomic techniques including epigenomics, and analysis of biomarkers of progression could functionally validate putative severity markers.
本综述将审视当前的证据，即基因和/或表观遗传变异可能影响多发性硬化症（MS）的临床病程、表型以及MS严重程度的指标，包括残疾进展和复发率。
几乎没有证据表明MS临床表型受显著的基因控制。越来越多的证据表明，可能存在残疾进展速率的基因决定因素。然而，能够分析残疾进展并考虑所有混杂变量（如治疗、临床特征和环境因素）的研究必然是纵向的、规模相对较小且通常持续时间较短，因此不适用于评估从全基因组关联研究（GWAS）获得的数十万基因变量。尽管如此，最近有证据支持基因位点与复发率的关联。最近的进展表明，基因变异可能与疾病严重程度相关，但与MS临床表型无关，但这些发现并不确定，有待重复验证。汇总研究结果、应用包括表观基因组学在内的其他基因组技术以及分析进展的生物标志物可以从功能上验证假定的严重程度标志物。
