Greater ozone exposure, genetic factors increase risk for pediatric MS
Ozone levels and DRB1 alleles represent independent factors that correlate with risk for pediatric MS, according to findings presented at MSVirtual2020.
The findings also showed that the odds of developing pediatric MS increased with higher exposure to ozone, especially in those carrying DRB1.
“MS is a complex disease,” Amin Ziaei, MD, a postdoctoral scholar in neurology at the University of California, San Francisco School of Medicine, said during his presentation. "Evidence [demonstrates] that there is a role for both genetic variants and environmental factors that increase MS risk.”
Ziaei and colleagues previously demonstrated a relationship between air pollutants and greater risk for pediatric MS. In the current study, they examined the relationship between ozone pollution and DRB1 status as the primary genetic variant associated with predisposition to MS.
The researchers analyzed data from patients with MS and healthy controls in the Environmental and Genetic Risk Factors for Pediatric MS study from the U.S. Network of Pediatric MS Centers. They collected county-level modeled ozone data from the CDC’s Environmental Public Health Tracking Network air pollution database and assigned participants ozone values based on their county of residence. They grouped the values into tertiles based on healthy controls. Ziaei and colleagues adjusted their analysis for sex, race, ethnicity, age, exposure to second-hand smoke and mother’s education level.
In total, Ziaei and colleagues included 355 pediatric patients with MS and 565 controls in their analysis.
They found that ozone levels independently correlated with pediatric MS risk in ozone tertile 2 (OR = 2.35; 95% CI, 1.57–3.51) and tertile 3 (OR = 2.21; 95% CI, 1.48–3.32) compared with the lowest tertile. The results also demonstrated an independent association between DRB1 status and risk for pediatric MS (OR = 1.99; 95% CI, 1.43-2.78).
Ziaei and colleagues observed a significant additive interaction between ozone levels and DRB1, with a relative excess risk due to interaction of 2.74 (95% CI, 0.5-4.98) and 2.43 (95% CI, 0.36-4.5) in the second and third tertiles, respectively. The researchers found that an estimated 60% of the pediatric MS risk among those with HLA-DRB1*15 haplotype and high ozone exposure could be attributed to the interaction between these risk factors.
“We found that the odds of having pediatric MS increased with higher exposure to the ozone, especially in those with DRB1 alleles,” Ziaei told Healio Neurology. “HLA-DRB1 is the main genetic risk factor for pediatric MS. We are working on assessing the gene-environmental interaction for other air pollutants.”
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It has long been observed that pediatric-onset MS, as well as adult-onset MS, is relatively common in industrialized areas. This study suggests one possible explanation: Exposure to ozone pollution was found to be a risk factor for development of pediatric MS, particularly in those individuals who carry a major genetic variant associated with MS susceptibility. Further research is needed to determine if a similar relationship exists in adult-onset MS. In addition, more research needs to be done to elucidate the underling molecular and cellular pathways that link air pollution with MS pathology.
Interestingly, stroke incidence and Alzheimer’s disease pathology have also been associated with air pollution. There is some evidence that pro-inflammatory molecules derived from interactions between the ozone and lung tissue can reach the central nervous system, where they activate microglia and astrocytes, and alter cerebral blood vessels, potentially triggering a destructive neuroinflammatory cascade.
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Ziaei A, et al. Abstract PS04.04. Presented at: MSVirtual2020; Sept. 11-13, 2020 (virtual meeting).
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