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Constellation of Factors Increase Risk of Multiple Sclerosis

Smoking, organic solvents, and genetic susceptibility combine to increase MS risk.

References1. Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: Interaction with MS risk HLA genes. Neurology. 2018;91:e455-e462.2. Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G, et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS One. 2012;7):e51506. doi: 10.1371/journal.pone.0051506.3. Bell JS, DeLuca GC. Genes, smoking, and organic solvent exposure: An alarming cocktail for MS risk. Neurology. 2018;91:199-200.

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Smoking, organic solvents, and genetic susceptibility combine to increase MS risk. A study by Hedström and colleagues[1] found that exposure to paint, varnishes, and other organic solvents may increase the risk of developing multiple sclerosis by about 50%, compared with unexposed individuals. Among people who carry a genetic variant that increase their susceptibility to MS, exposure to these toxins may increase their risk of MS by about 7 times, compared with unexposed people who don’t carry this gene. And, adding smoking to the equation increases the risk of developing MS approximately 30-fold, compared with unexposed people who don’t carry the gene and are nonsmokers.

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According to the CDC, "Millions of U.S. workers are exposed to organic solvents that are used in such products as paints, varnishes, lacquers, adhesives, glues, and degreasing/cleaning agents, and in the production of dyes, polymers, plastics, textiles, printing inks, agricultural products, and pharmaceuticals." Along with these solvents, new research has shed light on the interaction between genes, smoking, and the risk of developing multiple sclerosis (MS).[1]

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“These are significant interactions where the factors have a much greater effect in combination than they do on their own,” said study author Anna Hedström, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden in a press release. “More research is needed to understand how these factors interact to create this risk. It’s possible that exposure to solvents and smoking may both involve lung inflammation and irritation that leads to an immune reaction in the lungs,” she added.

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Several environmental factors have been linked to MS risk, including Epstein-Barr virus infection, Vitamin D, sun exposure habits, adolescent obesity, and smoking. Both smoking and organic solvents in paints and varnishes are lung irritants. Accumulating research has suggested that exposure to lung irritants may be a risk factor for autoimmune diseases like MS.[2]

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To study this idea, researchers conducted a case-control study that included 2042 adults newly diagnosed with MS and recruited from 40 neurology units across Sweden. Then they matched these cases by age, sex, and residential area with 2947 healthy controls randomly selected from the Swedish national population register. Participants self-reported environmental exposures and lifestyle information on standardized questionnaires. They also provided blood samples for analysis of HLA genes. Results were adjusted for age, sex, residential area, ancestry (Swedish vs non-Swedish) and smoking.

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•1.5 times increased odds of MS with exposure to organic solvents vs no exposure (OR 1.5, p = 0.0004)
•7 times increased odds of MS with exposure to organic solvents in carriers of HLA-DRB1*15 who lack HLA-A*02, vs nonexposed individuals without these genetic risk factors (OR 6.7, p<0.0001)
•30 times increased risk of MS in carriers of HLA-DRB1*15 who lack HLA-A*02, who smoke and were exposed to organic solvents, compared with non-exposed people without these genetic risk factors (OR 30.3, p<0.0001)
•Significant trend suggesting increased risk of MS with increasing length of exposure (p = 0.04) and total hours of exposure (p = 0.001).

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•Swedish epidemiological study found exposure to paint, varnishes and other organic solvents may increase the risk of MS by about 50%, compared to no exposure.
• People with genetic risk factors for MS who are exposed to these toxins may have 7 times increased risk of  MS, compared with unexposed people without these genetic risk factors 
• People with genetic risk factors for MS who smoked and were exposed to organic solvents had 30 times increased risk of MS, compared to unexposed nonsmokers without these genetic risk factors
• Lung irritation combined with genetic susceptibility could explain the findings, but further research is needed to understand the mechanism

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“How this cocktail of MS genes, organic solvents and smoking contributes so significantly to MS risk warrants investigation,” Gabriele C. DeLuca, MD, DPhil, and Jack Bell, BM, BCh, both of John Radcliffe Hospital (Oxford, UK), wrote in an accompanying editorial.[3] “In the meantime, avoiding cigarette smoke and unnecessary exposure to organic solvents, particularly in combination with each other, would seem reasonable lifestyle changes people can take to reduce the risk of MS, especially in people with a family history of the disease.” The authors mentioned several potential limitations, including self-reported exposure. Some participants may not have correctly remembered their exposures, which could have biased results.

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