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The interaction bet...
The interaction between smoking and HLA genes in multiple sclerosis : replication and refinement
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- Hedström, Anna Karin (author)
- Karolinska Institutet
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Katsoulis, Michail (author)
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- Hössjer, Ola (author)
- Stockholms universitet,Matematiska institutionen
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Bomfim, Izaura L. (author)
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Oturai, Annette (author)
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Bach Sondergaard, Helle (author)
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Sellebjerg, Finn (author)
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Ullum, Henrik (author)
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Wegner Thørner, Lise (author)
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Wendel Gustavsen, Marte (author)
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Harbo, Hanne F. (author)
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Obradovic, Dragana (author)
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Gianfrancesco, Milena A. (author)
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Barcellos, Lisa F. (author)
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Schaefer, Catherine A. (author)
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- Hillert, Jan (author)
- Karolinska Institutet
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- Kockum, Ingrid (author)
- Karolinska Institutet
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- Olsson, Tomas (author)
- Karolinska Institutet
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- Alfredsson, Lars (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-06-08
- 2017
- English.
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 23:1, s. 37-37
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Keyword
- Multiple sclerosis
- Smoking
- HLA
- Gene-environment interaction
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hedström, Anna K ...
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Katsoulis, Micha ...
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Hössjer, Ola
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Bomfim, Izaura L ...
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Oturai, Annette
-
Bach Sondergaard ...
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show more...
-
Sellebjerg, Finn
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Ullum, Henrik
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Wegner Thørner, ...
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Wendel Gustavsen ...
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Harbo, Hanne F.
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Obradovic, Draga ...
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Gianfrancesco, M ...
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Barcellos, Lisa ...
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Schaefer, Cather ...
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Hillert, Jan
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Kockum, Ingrid
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Olsson, Tomas
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Alfredsson, Lars
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Occupational Hea ...
- Articles in the publication
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European Journal ...
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MULTIPLE SCLEROS ...
- By the university
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Stockholm University
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Karolinska Institutet