PMID- 29970406 OWN - NLM STAT- MEDLINE DCOM- 20190821 LR - 20210317 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 91 IP - 5 DP - 2018 Jul 31 TI - Organic solvents and MS susceptibility: Interaction with MS risk HLA genes. PG - e455-e462 LID - 10.1212/WNL.0000000000005906 [doi] AB - OBJECTIVE: We 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. METHODS: 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. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction. RESULTS: Overall, 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. CONCLUSION: The 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. CI - Copyright (c) 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. FAU - Hedstrom, Anna Karin AU - Hedstrom AK AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. anna.hedstrom@ki.se. FAU - Hossjer, Ola AU - Hossjer O AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. FAU - Katsoulis, Michail AU - Katsoulis M AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. FAU - Kockum, Ingrid AU - Kockum I AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. FAU - Olsson, Tomas AU - Olsson T AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. FAU - Alfredsson, Lars AU - Alfredsson L AD - From the Department of Clinical Neuroscience and Institute of Environmental Medicine (A.K.H., L.A.), and Department of Clinical Neuroscience and Center for Molecular Medicine (I.K., T.O.), Karolinska Institutet, Stockholm; Mathematical Statistics (O.H.), Stockholm University, Sweden; UCL/Farr Institute of Health Informatics Research (M.K.), London, UK; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. LA - eng GR - FS/18/5/33319/BHF_/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180703 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (HLA-A*02 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB1*15 antigen) RN - 0 (Organic Chemicals) RN - 0 (Solvents) CIN - Neurology. 2018 Jul 31;91(5):199-200. PMID: 29970400 MH - Adult MH - Case-Control Studies MH - Environmental Exposure/*adverse effects MH - Female MH - *Gene-Environment Interaction MH - Genetic Predisposition to Disease/epidemiology/genetics MH - HLA-A2 Antigen/*genetics MH - HLA-DRB1 Chains/*genetics MH - Humans MH - Male MH - Middle Aged MH - Multiple Sclerosis/chemically induced/epidemiology/*genetics MH - Organic Chemicals/*adverse effects MH - Solvents/adverse effects MH - Sweden/epidemiology PMC - PMC6093765 EDAT- 2018/07/05 06:00 MHDA- 2019/08/23 06:00 PMCR- 2018/07/31 CRDT- 2018/07/05 06:00 PHST- 2017/10/24 00:00 [received] PHST- 2018/04/27 00:00 [accepted] PHST- 2018/07/05 06:00 [pubmed] PHST- 2019/08/23 06:00 [medline] PHST- 2018/07/05 06:00 [entrez] PHST- 2018/07/31 00:00 [pmc-release] AID - WNL.0000000000005906 [pii] AID - NEUROLOGY2017857789 [pii] AID - 10.1212/WNL.0000000000005906 [doi] PST - ppublish SO - Neurology. 2018 Jul 31;91(5):e455-e462. doi: 10.1212/WNL.0000000000005906. Epub 2018 Jul 3.