The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.

Autor: Hedström AK; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. anna.hedstrom@ki.se., Katsoulis M; UCL/Farr Institute of Health Informatics Research, London, UK., Hössjer O; Mathematical Statistics, Stockholm University, Stockholm, Sweden., Bomfim IL; Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Oturai A; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Sondergaard HB; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Sellebjerg F; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Ullum H; Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark., Thørner LW; Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark., Gustavsen MW; Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Harbo HF; Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Obradovic D; Department of Neurology, Military Medical Academy, Belgrade, Serbia., Gianfrancesco MA; Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, 94720-3220, USA., Barcellos LF; Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, 94720-3220, USA., Schaefer CA; Kaiser Permanente Division of Research, Oakland, CA, 94612, USA., Hillert J; Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden., Kockum I; Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden., Olsson T; Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden., Alfredsson L; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: European journal of epidemiology [Eur J Epidemiol] 2017 Oct; Vol. 32 (10), pp. 909-919. Date of Electronic Publication: 2017 Jun 08.
DOI: 10.1007/s10654-017-0250-2
Abstrakt: 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.
Databáze: MEDLINE
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