Global DNA Methylation and Global Hydroxymethylation in a Population-based Pilot Sample from the Strong Heart Study

Abstract

Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals. Aims: To evaluate the association between global DNA methylation and global DNA hydroxymethylation in a subsample of 48 Strong Heart Study participants who had selected metals measured in urine at baseline and DNA available in 1989-1991 and 1998-1999. Methods: Global 5-methylcytosine (5-mC) and 5-hydroxymethyl-cytosine (5-hmC) levels in DNA were measured by capture and detection antibodies followed by colorimetric quantification. We used linear regression models to evaluate trends and compare relative differences in methylation and hydroxymethylation levels by participant characteristics (age, sex, education, adiposity, smoking, alcohol intake, metal exposure and arsenic metabolism). Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p –value = 0.03) at visit 1 and 0.54 (p – value < 0.001) at visit 3, with consistent trends for both epigenetic markers across characteristics. The associations were significant for urine cadmium concentrations and global methylation and for arsenic metabolism and global hydroxymethylation. Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these epigenetic modifications and the characteristics evaluated suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.