Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford.
Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford.
Eur J Neurol. 2010 Sep;17(9):1210-1214. doi: 10.1111/j.1468-1331.2010.03003.x. Epub 2010 Mar 22.
The observation that the incidence of multiple sclerosis (MS) increases further from the equator has prompted considerable interest in the factors that might underlie this latitude gradient. Potential candidates include population frequencies of disease-associated Human Leukocyte Antigen (HLA) alleles which are the major genetic component of MS susceptibility. Ultraviolet (UV) exposure and smoking have also been implicated as key environmental risk factors.
We used multiple sources of published data on MS prevalence, HLA allele frequencies, UV index and cigarette smoking to assess the contributions of both nature and nurture to the distribution of MS within Europe.
We observed that HLA alleles unequivocally interact with a population-wide level to determine disease risk. The UV index and smoking behaviour was also shown to correlate with disease distribution in Europe. For countries with HLA, UV and smoking data, these three factors were shown to account for 75% of the variance in MS prevalence.
Genetic (HLA) and environmental (UV and smoking) risk factors thus interact in a complex manner with each other to determine a large proportion of MS susceptibility within Europe.
多发性硬化症（MS）的发病率从赤道地区进一步增加，这促使人们对可能构成这种纬度梯度的因素产生了极大的兴趣。潜在的候选因素包括与疾病相关的人类白细胞抗原（HLA）等位基因的人群频率，这些等位基因是 MS 易感性的主要遗传成分。紫外线（UV）暴露和吸烟也被认为是关键的环境风险因素。
我们使用了多发性硬化症患病率、HLA 等位基因频率、紫外线指数和吸烟情况的多个已发表数据来源，以评估先天和后天因素对欧洲内 MS 分布的影响。
我们观察到 HLA 等位基因与人群水平明确相互作用，决定疾病风险。紫外线指数和吸烟行为也与欧洲的疾病分布相关。对于具有 HLA、紫外线和吸烟数据的国家，这三个因素共同解释了 MS 患病率变异的 75%。
因此，遗传（HLA）和环境（紫外线和吸烟）风险因素以复杂的方式相互作用，决定了欧洲 MS 易感性的很大一部分。
