Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis (original) (raw)

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11 Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden

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22 Neuroimmunology Unit, Department of Clinical Neuroscience and Centre for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, 171 77 Solna, Sweden

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22 Neuroimmunology Unit, Department of Clinical Neuroscience and Centre for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, 171 77 Solna, Sweden

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11 Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden

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,

22 Neuroimmunology Unit, Department of Clinical Neuroscience and Centre for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, 171 77 Solna, Sweden

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,

22 Neuroimmunology Unit, Department of Clinical Neuroscience and Centre for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, 171 77 Solna, Sweden

Search for other works by this author on:

,

22 Neuroimmunology Unit, Department of Clinical Neuroscience and Centre for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, 171 77 Solna, Sweden

Search for other works by this author on:

11 Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden

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Received:

11 October 2010

Revision received:

15 November 2010

Accepted:

16 November 2010

Published:

08 February 2011

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Anna Karin Hedström, Emilie Sundqvist, Maria Bäärnhielm, Nina Nordin, Jan Hillert, Ingrid Kockum, Tomas Olsson, Lars Alfredsson, Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis, Brain, Volume 134, Issue 3, March 2011, Pages 653–664, https://doi.org/10.1093/brain/awq371
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Abstract

Both genetic and environmental factors display low or modest associations with multiple sclerosis. Hypothetically, gene–environment interactions may exert much stronger effects. In this study, we investigated potential interactions between genetic risk factors and smoking in relation to risk of developing multiple sclerosis. A population-based case–control study involving incident cases of multiple sclerosis (843 cases, 1209 controls) was performed in Sweden. Cases and controls were classified according to their smoking status and human leukocyte antigen DRB1 as well as human leukocyte antigen A genotypes. Subjects with different genotypes and smoking habits were compared with regard to incidence of multiple sclerosis, by calculating odds ratios with 95% confidence intervals employing logistic regression. The potential interaction between different genotypes, as well as between genotype and smoking, was evaluated by calculating attributable proportion due to interaction. A significant interaction between two genetic risk factors, carriage of human leukocyte antigen DRB1*15 and absence of human leukocyte antigen A*02, was observed among smokers whereas such an interaction was absent among non-smokers. There were considerable differences in odds ratios between the various groups. Compared with non-smokers with neither of the genetic risk factors, the odds ratio was 13.5 (8.1–22.6) for smokers with both genetic risk factors. The odds ratio for smokers without genetic risk was 1.4 (0.9–2.1) and the odds ratio for non-smokers with both genetic risk factors was 4.9 (3.6–6.6). Among those with both genetic risk factors, smoking increased the risk by a factor of 2.8 in comparison with a factor of 1.4 among those without the genetic risk factors. The risk of developing multiple sclerosis associated with human leukocyte antigen genotypes may be strongly influenced by smoking status. The findings are consistent with our hypothesis that priming of the immune response in the lungs may subsequently lead to multiple sclerosis in genetically susceptible people.

© The Author (2011). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Topic:

• smoking
• human leukocyte antigens
• disease transmission
• hla-a antigens
• multiple sclerosis
• genetic risk
• hla-drb1 gene

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