Passive smoking and genetic risks

Hedström AK, Bomfim IL, Barcellos LF, Briggs F, Schaefer C, Kockum I, Olsson T, Alfredsson L.Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.
Int J Epidemiol. 2014 Oct 15. pii: dyu195. [Epub ahead of print]

BACKGROUND: The recently described interaction between smoking, human leucocyte 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.


Following the creation of Glow-in-the-dark rats, which have a jellyfish gene that makes them fluorese under untra violet light, you had a tool to track immune cells that create neurological disease once they are injected into the blood a non-glow in the dark rat. Whilst they will go every where and will get filtered in the capillaries of the lungs, it seems that cells are supposed to actually traffick into the lungs through the lymph glands draining the lung before they go into the brain to cause disease.  Therefore anything that interferes with lung function may have consequences and in this study they looked at passive smoking as we all know that first hand smoking is bad for you and your pocket. We also know that MHC gene variants are associated with the risk of developing MS. If you had these gene variants you were 4 times more likely to develop MS, but seven timesmore likely if you were apassive smoker. Many of you will never of smoked but for many it would be hard never to be a passive smoker. Is this because of lymphocytes in the lungs being affected, a chance correlation, or something else?


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