Dataset Information

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).

SUBMITTER: Wang S

PROVIDER: S-EPMC4696784 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

Wang Shuo S Song Jieyun J Yang Yide Y Zhang Yining Y Wang Haijun H Ma Jun J

PloS one 20151230 12

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 assoc ...[more]

PMID: 26717317

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Project description:Offspring of persons exposed to childhood abuse are at higher risk of neurodevelopmental and physical health disparities across the life course. Animal experiments have indicated that paternal environmental stressors can affect sperm DNA methylation and gene expression in an offspring. Childhood abuse has been associated with epigenetic marks in human blood, saliva, and brain tissue, with statistically significant methylation differences ranging widely. However, no studies have examined the association of childhood abuse with DNA methylation in gametes. We examined the association of childhood abuse with DNA methylation in human sperm. Combined physical, emotional, and sexual abuse in childhood was characterized as none, medium, or high. DNA methylation was assayed in 46 sperm samples from 34 men in a longitudinal non-clinical cohort using HumanMethylation450 BeadChips. We performed principal component analysis and examined the correlation of principal components with abuse exposure. Childhood abuse was associated with a component that captured 6.2% of total variance in DNA methylation (p?<?0.05). Next, we investigated the regions differentially methylated by abuse exposure. We identified 12 DNA regions differentially methylated by childhood abuse, containing 64 probes and including sites on genes associated with neuronal function (MAPT, CLU), fat cell regulation (PRDM16), and immune function (SDK1). We examined adulthood health behaviors, mental health, and trauma exposure as potential mediators of an association between abuse and DNAm, and found that mental health and trauma exposure partly mediated the association. Finally, we constructed a parsimonious epigenetic marker for childhood abuse using a machine learning approach, which identified three probes that predicted high vs. no childhood abuse in 71% of participants. Our results suggested that childhood abuse is associated with sperm DNA methylation, which may have implications for offspring development. Larger samples are needed to identify with greater confidence specific genomic regions differentially methylated by childhood abuse.

Dataset Information

HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

Publications

HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

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