BLOOLD METHYLMICS IN RESPONSE TO ARSENIC EXPOSURE IN A LOW–EXPOSED US POPULATION

摘要

Exposure to arsenic (As) has been associated with cancers, CVD, and neurological disorder. To explore the possible underlying epigenetic mechanisms, a genome-wide study was conducted in low exposed healthy individuals. This study was nested within a prospective study of Coronary Artery Risk Development in Young Adults (CARDIA) by randomly selecting 46 non-smoker and non-diabetic White participants with low (N=23) and high (N=23) As exposure. based on toenail total As measures at examination year 2. We conducted methylomic profiling of white blood cell DNA collected at examination year 15 using the Illumina HumanMethylation450 BeadChip. Multivariate linear regression models were fitted to evaluate the associations between As exposure status and DNA methylation levels at each CpG site. We identified 29 CpG sites with methylation levels associated with As exposure status at a nominal p-value less than 0.0001. Some genes are known to be involved in cancers, CVD, and neurological disorder. Pathway analyses further revealed several canonical pathways relevant to the etiology of As-associated diseases. We demonstrated that As exposure is prospectively associated with DNA methylation levels in a number of genes implicated in As-associated diseases. Further studies are required for elucidating the role of epigenetic alterations in the pathogenesis of these diseases.