Mix of Organic Solvent Exposure, Smoking and Genes Raise Risk of MS by 30 Fold, Study Says

Exposure to organic solvents like such as paint or varnish greatly raises the risk of multiple sclerosis (MS), particularly in people who smoke or have a genetic susceptibility to the disease, a large-scale Swedish study reports.

In fact, solvent exposure — linked to occupation, like being a painter or working in a paint factory — raised risk by 50 percent compared to those with no such long-term exposure, and was higher still when smoking or genes also came into play. Exposure time, the number of years a person worked with paints or varnish, was not defined by the researchers.

The study, “Organic solvents and MS susceptibility, Interaction with MS risk HLA genes,” was published in the journal Neurology.

Multiple sclerosis (MS) is thought to develop in people based on a mix of genes and the environment.  The strongest genetic risk factors are variations localized in the human leukocyte antigen (HLA) genes: the HLA-DRB1*15 variant increases the likelihood of the disease by three times, while HLA-A*02 reduces the odds by half.

But a growing body of data  indicates that exposure to certain environmental factors also plays an essential role in determining risk. Factors here include Epstein-Barr virus infection, vitamin D status, sun exposure habits, adolescent obesity, and smoking.

When combined with a genetic predisposition, environmental harm may enlarge this existing risk of developing MS.

Researchers at the Karolinska Institutet in Sweden used a population-based case-control study to investigate the influence of occupational exposure to organic solvents — recently also suggested as an environmental factor — to the risk of developing MS. Synergistic links with genetic HLA variations and smoking habits were included in their investigation.

The team hypothesized that exposure to sources of lung irritation — smoking, paint or varnish fumes — may elicit an autoimmune response that can lead to MS in people with a genetic predisposition for the disease.

Data was collected from 2,042 MS patients and 2,947 controls (ages 16 to 70) from the general Swedish population. Information regarding environmental exposures and lifestyle factors, including occupation, was collected using a questionnaire. Blood samples were taken from participants to analyze genetic variations.

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The results showed that people who have been occupationally exposed to painting products, varnish, or other organic solvents were 50 percent more likely to develop MS than people without such exposure.

Reinforcing this association, data found that the longer the duration of exposure to organic solvents, the higher the probability of a person developing MS.

Importantly, the combination of organic solvent exposure and genetic predisposition and/or smoking sharply increased risk.

Those with solvent exposure and at-risk genes — the presence of HLA-DRB1*15 and absence of HLA-A*02 — the susceptibility to MS is almost seven times higher than in people with neither risk factor.

Adding being a smoker to the above skyrocketed risk. People who were in contact with organic solvents, smoked, and carried a genetic predisposition to MS had a 30 times higher risk of developing the MS — the most potent combination predisposing a person to MS found in the study.

“These are significant interactions where the factors have a much greater effect in combination than they do on their own,” Anna Hedström, MD, the study’s first author, said in a press release.

The researchers also found that genetic risk variants in combination to solvent exposure underlie some 60 percent of MS risk.

“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,” Hedström said.

An accompanying editorial by Gabriele C. DeLuca, a member of the American Academy of Neurology, called for research into the combination of risk factors — genes,  organic solvents and smoking — identified in this study.

“In the meantime,” DeLuca added,  a “reasonable lifestyle change” would be “avoiding cigarette smoke and unnecessary exposure to organic solvents, particularly in combination with each other.”