Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children

Autor: Cynthia A. Moylan, Alisha M. Mavis, Dereje Jima, Rachel Maguire, Mustafa Bashir, Jeongeun Hyun, Melanie N. Cabezas, Alice Parish, Donna Niedzwiecki, Anna Mae Diehl, Susan K. Murphy, Manal F. Abdelmalek, Cathrine Hoyo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Epigenetics, Vol 17, Iss 11, Pp 1446-1461 (2022)
Druh dokumentu: article
ISSN: 1559-2294
1559-2308
15592294
DOI: 10.1080/15592294.2022.2039850
Popis: Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90 mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7–12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3–13.4%) and MRE was 2.5 kPa (range, 1.5–3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR
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