Associations of children's urinary metals with blood RNA N6-methyladenosine and 2'-O-methyladenosine.

BACKGROUND

Post-transcriptional RNA modifications (the epitranscriptome) regulate gene expression and represent a pathway through which environmental exposures can affect health. Two RNA modifications important for health and disease are N6-methyladenosine (m6A) and 2'-O-methyladenosine (Am). However, the effects of metals and metalloids (hence, metals), on m6A and Am are less well understood. We aimed to investigate associations between children's metals exposures and global m6A and Am in blood.

METHODS

We measured essential (cobalt, copper, selenium, zinc) and nonessential (arsenic, cadmium, chromium, cesium, mercury, antimony) metals in urine and total m6A and Am in blood using liquid chromatography-tandem mass spectrometry in 150 children aged 9-11 in the Mexico City Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. We determined cross-sectional associations of log2-transformed metals mixtures with m6A and Am using quantile g-computation and linear regression.

RESULTS

Median m6A (expressed as %m6A/A) was 0.075 (interquartile range [IQR] 0.069, 0.079); median Am (%Am/A) was 2.53 (IQR 2.44, 2.66). Each quartile increase in the overall metal mixture was associated with a decrease of -0.095 (95 % confidence interval [CI] -0.15, -0.044) in %Am/A, adjusted for other metals, sex, age, visit date, and total RNA concentration. Each doubling of arsenic was associated with a decrease of -0.047 (-0.089, -0.0056) and each doubling in cesium was associated with a decrease of -0.096 (-0.18, -0.015) in %Am/A.

CONCLUSIONS

Exposure to nonessential metals may be related to global Am levels in children. Further research is warranted to evaluate potential roles of Am and m6A in metal-induced toxicity.