Exposure to Air Pollutants, Circulating miRNAs, and Cardiometabolic Health among Young Adults

Abstract

BACKGROUND AND AIM: Prior work has linked exposure to ambient air pollutants (AAP) with cardiometabolic risk factors in young adults. This association may be mediated by changes to microRNAs (miRNAs), which regulate gene expression. This study aimed to examine relationships between circulating miRNAs with AAP exposure and cardiometabolic risk factors in young adults. METHODS: Residential exposure to AAP (particulate matter 2.5 and 10 microns in aerodynamic diameter [PM2.5, PM10]; nitrogen dioxide [NO2]; 24-hour ozone [O3]) was modeled for 113 participants from the Metabolic and Asthma Incidence Research (Meta-AIR) Study, a cohort of young adults (17-22 years) from Southern California. NanoString technology was used to measure circulating miRNAs in serum. Multivariate linear regression was performed to examine the relationships between pre-selected circulating miRNAs (miR-146a-5p, miR-148a-3p, miR-126-3p, miR-122-5p), short-term (prior 1-month) and long-term (prior 1-year) AAP exposure, and cardiometabolic risk factors (e.g., fasting glucose, fasting insulin, lipids). Models adjusted for age, sex, and body mass index. Sex interactions were tested, and effects are reported for each standard deviation increase in exposure. RESULTS:Short-term O3 exposure was associated with greater expression of miR-148a-3p and miR-122-5p (β=12.7, p=0.01 and β=0.56, p=0.04, respectively). MiR-148a-3p (pinteractions=0.001) was also associated with triglycerides and VLDL among males (β=21.8, p=0.003 and β=4.4, p=0.003, respectively), but not females (β=0.7, p=0.90 and β=0.1, p=0.90, respectively). Long-term O3 exposure was positively associated with miR-146a-5p (β=19.6, p=0.04) and miR-146a-5p was inversely associated with fasting glucose levels (β=-2.0, p=0.03). Short-term PM2.5 was inversely associated with miR-126-3p (β=-195.4, p=0.04) and miR-126-3p was also modestly inversely associated with fasting glucose levels (β=-1.7, p=0.06). CONCLUSIONS:Circulating miRNAs with putative gene targets involved in hepatic lipid metabolism (miR-122-5p, miR-148a-3p), NFκβ signaling (miR-146a), and insulin signaling (miR-126-3p) were associated with residential AAP exposure among young adults. Results suggest that miRNA expression may be a mechanistic link between AAP and cardiometabolic disease risk. KEYWORDS: Air pollution, Particulate matter, Obesity and metabolic disorders, Environmental epidemiology, Molecular epidemiology