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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: DNA methylation of extracellular matrix remodeling genes in children exposed to arsenic.

Authors: Gonzalez-Cortes, Tania; Recio-Vega, Rogelio; Lantz, Robert Clark; Chau, Binh T

Published In Toxicol Appl Pharmacol, (2017 Aug 15)

Abstract: Several novel mechanistic findings regarding to arsenic's pathogenesis has been reported and some of them suggest that the etiology of some arsenic induced diseases are due in part to heritable changes to the genome via epigenetic processes such as DNA methylation, histone maintenance, and mRNA expression. Recently, we reported that arsenic exposure during in utero and early life was associated with impairment in the lung function and abnormal receptor for advanced glycation endproducts (RAGE), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) sputum levels. Based on our results and the reported arsenic impacts on DNA methylation, we designed this study in our cohort of children exposed in utero and early childhood to arsenic with the aim to associate DNA methylation of MMP9, TIMP1 and RAGE genes with its protein sputum levels and with urinary and toenail arsenic levels. The results disclosed hypermethylation in MMP9 promotor region in the most exposed children; and an increase in the RAGE sputum levels among children with the mid methylation level; there were also positive associations between MMP9 DNA methylation with arsenic toenail concentrations; RAGE DNA methylation with iAs, and %DMA; and finally between TIMP1 DNA methylation with the first arsenic methylation. A negative correlation between MMP9 sputum levels with its DNA methylation was registered. In conclusion, arsenic levels were positive associated with the DNA methylation of extracellular matrix remodeling genes;, which in turn could modifies the biological process in which they are involved causing or predisposing to lung diseases.

PubMed ID: 28579250 Exiting the NIEHS site

MeSH Terms: Age Factors; Arsenic Poisoning/diagnosis; Arsenic Poisoning/genetics*; Arsenic Poisoning/urine; Arsenic/adverse effects*; Child; DNA Methylation/drug effects*; Extracellular Matrix/metabolism*; Female; Genetic Markers; Humans; Male; Maternal Exposure/adverse effects; Matrix Metalloproteinase 9/genetics*; Matrix Metalloproteinase 9/metabolism; Matrix Metalloproteinase 9/urine; Nails/chemistry; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Receptor for Advanced Glycation End Products/genetics*; Receptor for Advanced Glycation End Products/metabolism; Risk Assessment; Sputum/chemistry; Tissue Inhibitor of Metalloproteinase-1/genetics*; Tissue Inhibitor of Metalloproteinase-1/metabolism; Tissue Inhibitor of Metalloproteinase-1/urine; Water Pollutants, Chemical/adverse effects*; Water Supply

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