AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children.
Date
2023-10
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
Background
Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.Methods
We assessed metabolic dysfunction using liver fat content (LFC), serum, and clinical data in children aged 7-12 years (n=78) followed since birth. Maternal smoking was self-reported at 12 weeks gestation. Methylation was measured by means of pyrosequencing at 3 sequential CpG sites, including cg05575921, at birth and at ages 7-12. Regression models were used to evaluate whether AHRR methylation mediated the association between maternal smoking and child metabolic dysfunction.Results
Average AHRR methylation at birth was significantly higher among children of nonsmoking mothers compared with children of mothers who smoked (69.8% ± 4.4% vs. 63.5% ± 5.5, p=0.0006). AHRR hypomethylation at birth was associated with higher liver fat content (p=0.01), triglycerides (p=0.01), and alanine aminotransferase levels (p=0.03), and lower HDL cholesterol (p=0.01) in childhood. AHRR hypomethylation significantly mediated associations between maternal smoking and liver fat content (indirect effect=0.213, p=0.018), triglycerides (indirect effect=0.297, p=0.044), and HDL cholesterol (indirect effect = -0.413, p=0.007). AHRR methylation in childhood (n=78) was no longer significantly associated with prenatal smoke exposure or child metabolic parameters (p>0.05).Conclusions
AHRR hypomethylation significantly mediates the association between prenatal tobacco smoke exposure and features of childhood metabolic dysfunction, despite the lack of persistent hypomethylation of AHRR into childhood. Further studies are needed to replicate these findings and to explore their causal and long-term significance.Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Vidal, Adriana C, Shivram A Chandramouli, Joddy Marchesoni, Nia Brown, Yukun Liu, Susan K Murphy, Rachel Maguire, Yaxu Wang, et al. (2023). AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children. Hepatology communications, 7(10). p. e0243. 10.1097/hc9.0000000000000243 Retrieved from https://hdl.handle.net/10161/30399.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Susan Kay Murphy
Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist with training in human epigenetics, her research interests are largely centered around the role of epigenetic modifications in health and disease.
Dr. Murphy has ongoing projects on gynecologic malignancies, including approaches to eradicate ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease. Dr. Murphy is actively involved in many collaborative projects relating to the Developmental Origins of Health and Disease (DOHaD).
Her lab is currently working on preconception environmental exposures in males, particularly on the impact of cannabis on the sperm epigenome and the potential heritability of these effects. They are also studying the epigenetic and health effects of in utero exposures, with primary focus on children from the Newborn Epigenetics STudy (NEST), a pregnancy cohort she co-founded who were recruited from central North Carolina between 2005 and 2011. Dr. Murphy and her colleagues continue to follow NEST children to determine relationships between prenatal exposures and later health outcomes.
Mustafa Shadi Rifaat Bashir
Hepatobiliary and pancreatic imaging
Liver cancer (hepatocellular carcinoma)
Fatty liver, NAFLD, and NASH
Chronic liver disease and cirrhosis
Pancreatic cancer
Technical development in MRI
Quantitative imaging
Cynthia Ann Moylan
My research interests focus on the study of chronic liver disease and primary liver cancer, particularly from metabolic dysfunction associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease (NAFLD). As part of the MASLD Research Team at Duke, we are investigating the role of environmental contaminants, epigenetics, and genetics on the development of advanced fibrosis and liver cancer from MASLD and other chronic liver diseases. We are also interested in understanding risks for progressive liver disease including developmental programming and in utero exposures and have been investigating these risks through studies of the Newborn Epigenetics Study (NEST). The long term goal of our research is to develop non-invasive biomarkers to identify those patients at increased risk for cirrhosis and end stage liver disease in order to risk stratify patients as well as to develop better preventative and therapeutic strategies.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.