Hedström Anna Karin, Bomfim Izaura Lima, Barcellos Lisa F, Briggs Farren, Schaefer Catherine, Kockum Ingrid, Olsson Tomas, Alfredsson Lars
Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden
Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
Int J Epidemiol. 2014 Dec;43(6):1791-8. doi: 10.1093/ije/dyu195. Epub 2014 Oct 15.
The recently described interaction between smoking, human leukocyte antigen (HLA) DRB115 and absence of HLA-A02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype.
We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction.
An interaction was observed between passive smoking and carriage of HLA-DRB115 (AP 0.3, 95% CI 0.02-0.5 in the incident study, and AP 0.4, 95% CI 0.1-0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3-6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5-10.8).
The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.
最近描述的吸烟、人类白细胞抗原（HLA）DRB115以及缺乏HLA - A02与多发性硬化症（MS）风险之间的相互作用表明，吸烟所带来的风险因遗传背景而异。我们旨在研究被动吸烟与HLA基因型之间是否存在类似的相互作用。
我们使用了一项针对MS新发病例的病例对照研究（736例病例，1195例对照）和一项针对现患病例的研究（575例病例，373例对照）。通过计算具有95%置信区间（CI）的比值比（OR），比较了具有不同基因型和被动吸烟状态的从不吸烟者患MS的情况。通过计算因相互作用导致的归因比例（AP）来评估不同基因型与被动吸烟之间的潜在相互作用。
观察到被动吸烟与携带HLA - DRB115之间存在相互作用（在新发病例研究中AP为0.3，95%CI为0.02 - 0.5；在现患病例研究中AP为0.4，95%CI为0.1 - 0.7），以及被动吸烟与缺乏HLA - A02之间也存在相互作用。与没有这两种遗传风险因素的非吸烟者相比，具有这两种风险基因型的未暴露受试者的OR为4.5（95%CI为3.3 - 6.1），而暴露于被动吸烟的相同基因型受试者的OR为7.7（95%CI为5.5 - 10.8）。
与不同HLA基因型相关的患MS风险可能受到被动吸烟暴露的影响。这一发现支持了我们的假设，即肺部免疫反应的启动可能随后导致对该疾病具有遗传易感性的人患MS。
