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The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.
Anna Karin Hedström1, Michail Katsoulis2, Ola Hössjer3
1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. anna.hedstrom@ki.se.
European Journal of Epidemiology
|June 10, 2017
Summary
Smoking and specific human leukocyte antigen (HLA) genotypes significantly interact to increase multiple sclerosis (MS) risk. Smokers with HLA-DRB1*15 and lacking HLA-A*02 face a 13-fold higher risk, highlighting smoking
Area of Science:
- Immunogenetics
- Environmental Epidemiology
- Neurology
Background:
- Multiple sclerosis (MS) etiology is complex, involving gene-environment interactions.
- Previous studies suggested an interaction between smoking and HLA genotype in MS development.
- Replication and extension of these findings across diverse populations are crucial.
Purpose of the Study:
- To replicate and refine the observed interaction between smoking and HLA genotype in MS risk.
- To extend these findings to multiple international populations.
- To investigate potential three-way interactions between smoking, HLA-DRB1*15, and HLA-A*02.
Main Methods:
- Pooled analysis of six independent case-control studies from five countries (Sweden, Denmark, Norway, Serbia, USA).
- Detailed analysis combining genetically similar Nordic populations.
- Statistical analysis to identify two-way and three-way interactions between smoking and specific HLA alleles (HLA-DRB1*15, HLA-A*02).
Main Results:
- Replicated the interaction between smoking and HLA genotype in MS risk across pooled and Nordic populations.
- Identified significant two-way interactions between smoking and HLA-DRB1*15, and between smoking and HLA-A*02.
- Observed a significant three-way interaction, with smokers carrying HLA-DRB1*15 and lacking HLA-A*02 having a 13-fold increased MS risk compared to non-smokers without these genetic factors.
- Demonstrated that the influence of HLA genotype on MS risk is strongly modulated by smoking status, and vice versa.
Conclusions:
- The interaction between smoking and HLA genotype is a significant factor in MS development, consistent across multiple populations.
- Smoking appears to modify MS risk by influencing adaptive immunity, given the role of HLA molecules in antigen presentation.
- These findings underscore the importance of considering gene-environment interactions in understanding MS pathogenesis and developing targeted prevention strategies.
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