Air pollution exposure and mitochondrial DNA copy number in the UK Biobank

Abstract

ABSTRACTBackgroundLow levels of mitochondrial DNA copy number (mtDNA-CN) are a biomarker of mitochondrial dysfunction often induced by oxidative stress. Air pollution is a pervasive source of oxidative stress, but the association between air pollution exposure and mtDNA-CN is inconclusive.ObjectiveWe evaluated the association between long-term exposure to PM ≤ 10 µm diameter (PM10) and nitrogen dioxide (NO2) with mtDNA-CN in 195,196 adults in the UK Biobank study.MethodsAnnual average PM10 and NO2 concentrations were estimated using separate land-use regression models for years 2007 and 2010. mtDNA-CN was measured in blood samples collected between 2007 and 2010 and was calculated as the ratio of mitochondrial coverage to the nuclear genome coverage derived from whole-genome sequencing in 195,196 UK Biobank participants. We used standardized values (Z-scores) after log-transformation as the mtDNA-CN metric.ResultsThe median (interquartile range) annual average concentrations of PM10 and NO2 were 21.8 (20.3–23.6) and 28.9 (23.7–35.1) µg/m3 in 2007, and 16.2 (15.5–17.1) and 27.8 (22.7–32.4) µg/m3 in 2010. An increase of 10 µg/m3 in annual average PM10 and NO2 exposure was associated with an adjusted difference in mtDNA-CN of −0.089 (95% confidence interval; −0.090, −0.087) and −0.018 (−0.018, −0.017), respectively. The associations persisted for lags of up to 3 years. PM2.5-10 was also inversely associated with mtDNA-CN.ConclusionsIn this large-scale study, long-term exposure to PM10 and NO2 were inversely associated with mtDNA-CN. These findings suggest that oxidative stress-induced mitochondrial dysfunction, reflected by reduced mtDNA-CN, may be an additional mechanism mediating the health effects of air pollution.