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. 2014 Dec;43(6):1791-8.
doi: 10.1093/ije/dyu195. Epub 2014 Oct 15.

Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk

Anna Karin Hedström  1 , Izaura Lima Bomfim  2 , Lisa F Barcellos  2 , Farren Briggs  2 , Catherine Schaefer  2 , Ingrid Kockum  2 , Tomas Olsson  2 , Lars Alfredsson  2
Affiliations

Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk

Anna Karin Hedström et al. Int J Epidemiol. 2014 Dec.

Abstract

Background: The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype.

Methods: We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction.

Results: An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02-0.5 in the incident study, and AP 0.4, 95% CI 0.1-0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3-6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5-10.8).

Conclusions: The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.

Keywords: HLA genotype; Multiple sclerosis; case-control study; gene-environment interaction; immunology; passive smoking; smoking.

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Figures

Figure 1.
Figure 1.
ORs with 95% CIs for never-smokers with different combinations of HLA-DRB1*15 and HLA-A*02 status and exposure to passive smoking. Based on EIMS and the KPNC study. Statistics are shown in Table 4 .
See this image and copyright information in PMC

References

    1. Lincoln MR, Montpetit A, Cader MZ, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005;37:1108–12. - PubMed
    1. Brynedal B, Duvefelt K, Jonasdottir G, et al. HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis. PLoS One 2007;2:e664. - PMC - PubMed
    1. International Multiple Sclerosis Genetics Consortium (IMSGC). Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214-219. - PMC - PubMed
    1. Hedström AK, Hillert J, Olsson T, Alfredsson L. Smoking and multiple sclerosis susceptibility. Eur J Epidemiol 2013;28:867–74 - PMC - PubMed
    1. Hedström AK, Sundqvist E, Bäärnhielm M, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain 2011;134:653–64. - PubMed

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