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Interaction Between Ozone Pollution and Gene Alleles May Increase MS Risk

A strong interaction between ozone pollution exposure and positivity for the HLA-DRB1*15 alleles boosts the risk of multiple sclerosis (MS) development in pediatric cohorts, researchers reported at the MS Virtual 2020 meeting, a joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis.

Amin Ziaei, MD, PhD, a post-doctoral research fellow at the University of California, San Francisco, and colleagues wanted to assess the interaction between DRB1*15 status—the primary genetic variant linked with MS susceptibility—and ozone pollution.

"Our results suggest avoiding ozone exposure… as a lifestyle modification approach for MS," Dr. Ziaei said. The identification of a molecular mechanism underlying ozone exposure and increased MS risk may have potential implications for therapy in the future, he added.

However, he pointed out it is premature to conclude that clinicians need to test children for these alleles at this time.

In the study involving 355 cases and 565 controls who were enrolled by the US Network of Pediatric MS Centers, the odds of having pediatric MS increased with higher exposure to ozone, especially among those with the alleles,  Dr. Ziaei told Neurology Today At the Meetings.

Researchers used county-level data from the Centers for Disease Control and Prevention's Environmental Tracking Network air pollution database. The ozone values for subjects were based on their residence at the time of their enrollment in the study.

Researchers divided the exposure levels into tertiles and calculated an additive interaction between ozone and DRB1 of 2.74 for the tertile with the most ozone exposure, and 2.43 for the middle exposure group. They calculated that 60 percent of the disease measured among participants could be attributed to this additive interaction, Dr. Ziaei said.

Ozone exposure could be impacting MS risk in different ways, Dr. Ziaei said. It could have an effect on inflammation and oxidative insult in the CNS, modulating the immune system with an impact on the myelin sheath, Dr. Ziaei said. "This could cause CNS autoimmunity and CNS autoantigens," Dr. Ziaei said. "HLA-DRB1*15 alleles in immune cells have a high affinity to CNS autoantigens. That could cause this interaction between ozone exposure and HLA DRB-1."

Mitchell T. Wallin, MD, MPH, FAAN, associate professor of neurology at George Washington University and the University of Maryland, said the study is pursuing an important question but more details would be helpful.

"I agree with the premise that we have to understand what's going in the environment that can be driving MS. It's important to be looking at these factors," he said. "They found a risk, and I think it's important to point this out."

But the researchers did not report the length of exposure time. They grouped them by exposure level based on their county of residence at a particular time.

"I would think you would have to be exposed to this kind of pollutant for a certain amount of time before it's going to have an impact on your risk for developing MS," he said. "They probably need to do a little bit more work on time and amount of exposure within the cohort."

Drs. Ziaei and Wallin have no relevant disclosures.

Link Up for Related Information:

MS Virtual 2020 Abstract PS04.04: Ziaei A, Lavery A, Adams C, et al. Evidence for an interaction between ozone pollution and HLA-DRB1*15 alleles in pediatric multiple sclerosis.

Palacios N, Munger KL, Fitzgerald KC, et al. Exposure to particulate matter air pollution and risk of multiple sclerosis in two large cohorts of US nurses. Environ Int 2017;109:64-72.