Neuroimmunology Unit, Center for Molecular Medicine, L8:04, Karolinska University Hospital (Solna), 17176 Stockholm, Sweden.
Genetic Epidemiology and Genomics Laboratory, California Institute for Quantitative Biosciences (QB3), Office: 308D Stanley Hall, University of California, Berkeley, CA 94720-3220.
Nat Rev Neurol. 2017 Jan;13(1):25-36. doi: 10.1038/nrneurol.2016.187. Epub 2016 Dec 9.
Genetic predisposition to multiple sclerosis (MS) only explains a fraction of the disease risk; lifestyle and environmental factors are key contributors to the risk of MS. Importantly, these nongenetic factors can influence pathogenetic pathways, and some of them can be modified. Besides established MS-associated risk factors - high latitude, female sex, smoking, low vitamin D levels caused by insufficient sun exposure and/or dietary intake, and Epstein-Barr virus (EBV) infection - strong evidence now supports obesity during adolescence as a factor increasing MS risk. Organic solvents and shift work have also been reported to confer increased risk of the disease, whereas factors such as use of nicotine or alcohol, cytomegalovirus infection and a high coffee consumption are associated with a reduced risk. Certain factors - smoking, EBV infection and obesity - interact with HLA risk genes, pointing at a pathogenetic pathway involving adaptive immunity. All of the described risk factors for MS can influence adaptive and/or innate immunity, which is thought to be the main pathway modulated by MS risk alleles. Unlike genetic risk factors, many environmental and lifestyle factors can be modified, with potential for prevention, particularly for people at the greatest risk, such as relatives of individuals with MS. Here, we review recent data on environmental and lifestyle factors, with a focus on gene-environment interactions.
遗传易感性仅能解释多发性硬化症 (MS) 风险的一小部分；生活方式和环境因素是 MS 风险的关键因素。重要的是，这些非遗传因素可以影响发病途径，其中一些因素可以被改变。除了已确定的与 MS 相关的风险因素——高纬度、女性、吸烟、因日晒不足和/或饮食摄入导致的维生素 D 水平低以及 Epstein-Barr 病毒 (EBV) 感染——目前有强有力的证据表明青春期肥胖是增加 MS 风险的一个因素。有机溶剂和轮班工作也被报道与疾病风险增加有关，而尼古丁或酒精使用、巨细胞病毒感染和高咖啡摄入量等因素与风险降低有关。某些因素——吸烟、EBV 感染和肥胖——与 HLA 风险基因相互作用，表明涉及适应性免疫的发病途径。MS 的所有描述风险因素都可以影响适应性和/或先天免疫，这被认为是 MS 风险等位基因调节的主要途径。与遗传风险因素不同，许多环境和生活方式因素可以被改变，具有预防的潜力，特别是对那些处于最大风险的人群，如 MS 患者的亲属。在这里，我们回顾了环境和生活方式因素的最新数据，重点关注基因-环境相互作用。
