Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.
Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.
复制标题
DOI：
10.1093/ije/dyu195
复制
发表时间：
2014-12
影响因子：
7.7
通讯作者：
Alfredsson L
中科院分区：
文献类型：
--
作者：
Hedström AK;Bomfim IL;Barcellos LF;Briggs F;Schaefer C;Kockum I;Olsson T;Alfredsson L
背景：最近描述的吸烟、人类白细胞抗原 (HLA) DRB1*15 和 HLA-A*02 缺失与多发性硬化症 (MS) 风险之间的相互作用表明，吸烟带来的风险因遗传背景而异。我们的目的是调查被动吸烟和 HLA 基因型之间是否存在类似的相互作用。方法：我们使用了一项针对多发性硬化症发病病例（736 例，1195 例对照）的病例对照研究和一项针对流行病例（575 例，373 例对照）的病例对照研究。通过计算比值比 (OR) 和 95% 置信区间 (CI)，比较具有不同基因型和被动吸烟状况的从不吸烟者的 MS 发生率。通过计算交互作用的归因比例（AP）来评估不同基因型与被动吸烟之间的潜在交互作用。结果：观察到被动吸烟与 HLA-DRB1*15 携带之间存在相互作用（事件研究中 AP 0.3，95% CI 0.02-0.5，流行研究中 AP 0.4，95% CI 0.1-0.7），以及被动吸烟与 HLA-A*02 缺失之间存在相互作用。与没有这两种遗传风险因素中任何一种的非吸烟者相比，具有两种风险基因型的未暴露受试者的 OR 为 4.5 (95% CI 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 5.5–10.8)。结论：与不同 HLA 基因型相关的 MS 风险可能受到被动吸烟的影响。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罹患多发性硬化症。
Background: The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 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. Methods: 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. Results: An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (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-A*02. 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). Conclusions: 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.