title: HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.
abstract: Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05), and found positive associations between methylation and alanine aminotransferase (ALT) levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007). These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Yide
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood*; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D063766:Pediatric Obesity / Q000097:blood* / Q000235:genetics*; D012097:Repressor Proteins
chemical_list: D000410:Alanine Transaminase; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D012097:Repressor Proteins; C116973:HIF3A protein, human