The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.
The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.
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DOI：
10.1007/s10654-017-0250-2
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发表时间：
2017-10
影响因子：
13.6
通讯作者：
Alfredsson L
中科院分区：
文献类型：
--
作者：
Hedström AK;Katsoulis M;Hössjer O;Bomfim IL;Oturai A;Sondergaard HB;Sellebjerg F;Ullum H;Thørner LW;Gustavsen MW;Harbo HF;Obradovic D;Gianfrancesco MA;Barcellos LF;Schaefer CA;Hillert J;Kockum I;Olsson T;Alfredsson L
环境和遗传之间的相互作用可能有助于多发性硬化症（MS）的发展。我们调查了先前在瑞典人群中观察到的吸烟和HLA基因型之间的相互作用是否可以复制，改进和扩展到包括其他人群。我们使用了来自5个不同国家（瑞典、丹麦、挪威、塞尔维亚、美国）的6项独立病例对照研究。对先前观察结果进行了汇总分析（7190例病例，8876例对照）。通过结合来自北欧研究的遗传相似人群（6265例，8401例对照）进行了精细的详细分析。在合并分析和北欧合并材料中，观察到HLA-DRB*15与HLA-A*02缺失之间以及吸烟与每个遗传风险因素之间的相互作用。在三个变量的每个组合之间观察到双向相互作用，在第三个类别上不变。此外，风险因素之间也存在三种相互作用。携带HLA-DRB 1 *15和缺乏HLA-A*02的吸烟者与不携带这些遗传风险因素的从不吸烟者相比，MS风险增加了13倍（OR 12.7，95%CI 10.8-14.9）。与HLA基因型相关的MS风险受到吸烟状况的强烈影响，反之亦然。由于HLA分子的功能是将肽抗原呈递给T细胞，所展示的相互作用强烈表明吸烟通过对适应性免疫的作用改变MS风险。本文的在线版本（doi：10.1007/s10654-017-0250-2）包含补充材料，可供授权用户使用。
Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8–14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity. The online version of this article (doi:10.1007/s10654-017-0250-2) contains supplementary material, which is available to authorized users.
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影响因子：
7.7
作者：
Hedström AK;Bomfim IL;Barcellos LF;Briggs F;Schaefer C;Kockum I;Olsson T;Alfredsson L
通讯作者：
Alfredsson L
影响因子：
3.7
作者：
Petti S;Masood M;Scully C
通讯作者：
Scully C
影响因子：
11.2
作者：
Polman CH;Reingold SC;Banwell B;Clanet M;Cohen JA;Filippi M;Fujihara K;Havrdova E;Hutchinson M;Kappos L;Lublin FD;Montalban X;O'Connor P;Sandberg-Wollheim M;Thompson AJ;Waubant E;Weinshenker B;Wolinsky JS
通讯作者：
Wolinsky JS
影响因子：
14.5
作者：
Hedstrom, Anna Karin;Sundqvist, Emilie;Alfredsson, Lars
通讯作者：
Alfredsson, Lars
影响因子：
5.4
作者：
Lucca, Liliana E.;Axisa, Pierre-Paul;Liblau, Roland S.
通讯作者：
Liblau, Roland S.