Abstract
ObjectiveWe hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes.MethodsUsing a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction.ResultsOverall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2–1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB1*15, and absence of HLA-A*02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.ConclusionThe mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.
Highlights
Among both ever and never smokers, an interaction between organic solvents, carriage of human leukocyte antigen (HLA)-DRB1*15, and absence of HLA-A*02 was observed with regard to multiple sclerosis (MS) risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure
Our analysis of exposure to organic solvents and MS risk was based on 2,042 cases and 2,947 controls matched by age, sex, and residential area
A significant association was observed between exposure to organic solvents and increased risk of developing MS
Summary
Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. Study design and study participants This study was based on Epidemiological Investigation of Multiple Sclerosis, which is a Swedish population-based casecontrol study comprising the general population aged 16 to 70 years. Diagnosed cases with MS were recruited via 40 neurology units, including all Swedish university hospitals. Two controls per case were randomly selected from the national population register (density sampling), frequency matched for the case’s age in 5-year age strata, sex, and residential area. The study participants were recruited between April 2005 and December 2013. More detailed descriptions of study design and methods are given elsewhere.[13]
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