DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.
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2021-05-19
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Abstract
Background
Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.Objective
This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.Methods
Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure.Results
Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44).Discussion
Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.Type
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Fuemmeler, Bernard F, Mikhail G Dozmorov, Elizabeth K Do, Junfeng Jim Zhang, Carole Grenier, Zhiqing Huang, Rachel L Maguire, Scott H Kollins, et al. (2021). DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study. Environmental health perspectives, 129(5). p. 57010. 10.1289/ehp8099 Retrieved from https://hdl.handle.net/10161/23417.
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Junfeng Zhang
Dr. Zhang joined the Duke Faculty in fall 2013 from the University of Southern California where he had been a professor of environmental and global health and the director of Environmental and Biomarkers Analysis Laboratory since 2010. His prior positions include professor, department chair, and associate dean at the Rutgers School of Public Health. Dr. Zhang has more than 290 peer-reviewed publications. His work has been featured in major international media such as the Time, the New York Times, BBC, ABC, CBS, Yahoo News, etc. His early work on characterizing sources of non-methane greenhouse gases made him one of the officially recognized contributor to the 2007 Nobel Peace Prize awarded to IPCC. He is the 2012 recipient of the Jeremy Wesolowski Award, the highest award of the International Society of Exposure Science. He also received a Distinguished Alumni Award from the Rutgers Graduate School.
Dr. Zhang’s research interests include developing novel biomarkers of human exposure and health effects, assessing health and climate co-benefits of air pollution interventions, and examining biological mechanisms by which environmental exposures exert adverse health effects. Dr. Zhang has led a number of international collaborations to study air pollution health effects and underlying pathophysiologic mechanisms. These studies integrate epidemiological and toxicological approaches into natural experiment designs. He has conducted several indoor air purification intervention studies to evaluate the effectiveness of personal exposure reduction in improving health outcomes in China. Currently, he is conducting intervention trials of residential air purification in older adults with a heart disease history and adults at risk for Type 2 diabetes living in Los Angels where air pollution levels are high. He is co-leading a project to study whether and how particulate matter pollution affects respiratory viral infections in two cities of Mongolia.
Zhiqing Huang
Dr. Huang is an Assistant Professor in the Department of Obstetrics and Gynecology, Division of Reproductive Sciences, at Duke University Medical Center. She obtained her MD at North China Coal Medical University in China and her PhD at the University of Heidelberg in Germany under the mentorship of Dr. Ralph Witzgall. She did her postdoctoral training with Dr. Jiemin Wong at Baylor College of Medicine, studying how histone methylation and chromatin modifications regulate androgen receptor transcription.
Dr. Huang’s research includes the following:
•The factors in the tumor microenvironment contribute to ovarian cancer progress;
•New drug development for recurrent ovarian cancer treatment;
•The early DNA methylation profiles contribute to cancer development in late life;
•The special changes in the tumor microenvironment;
•Epigenetics and epigenomics.
*The impact of lipid metabolism in the tumor microenvironment in cancer progression and treatment.
*Impact of ferroptosis in endometriosis development.
Dr. Huang has received an R03 funding titled “Role of Age-Related Changes in the Tumor Microenvironment on Ovarian Cancer Progression” from NIA at NIH for 2021-2023.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2022, for a project titled "Single Cell Spatial Transcriptomics in Highly Aggressive and Less Aggressive Ovarian Cancer".
Dr. Huang has received Duke Cancer Institute 2023 spring pilot study award for07012023-06302024, the project title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence”.
Dr. Huang has received the American Cancer Society -Duke Cancer Institute (ASC-DCI) 2024 spring pilot study award for 07012024-06302025. The project title is "Early Establishment of Epigenetic Profiles that Increase Cancer Risk in Late Life”.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2023 for 01012024-12312024. The project's title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence".
Scott Haden Kollins
Scott H. Kollins, PhD received his undergraduate degree in psychology from Duke and his Master’s and Doctorate degrees in Clinical Psychology from Auburn University. After completing his clinical internship at the University of Mississippi Medical Center, where he served as Chief Intern, he joined the faculty of the Department of Psychology at Western Michigan University for three years, before joining the Duke faculty in 2000. Dr. Kollins has published more than 125 scientific papers in peer-reviewed journals. Over the past 10 years, his research has been supported by 6 different federal agencies, including NICHD, NIDA, NIMH, NIEHS, NINDS, and EPA, and he currently holds a mid-career K24 award from NIDA. He has also served as PI on more than 40 industry-funded clinical trials and is a consultant to a number of pharmaceutical companies in the area of ADHD clinical psychopharmacology. He has served as a standing member of the Child Psychopathology and Developmental Disabilities study section and also served as an ad-hoc reviewer for 10 additional NIH study sections and 7 international granting agencies. He is an Associate Editor for the Journal of Attention Disorders and has reviewed for more than 50 different peer-reviewed journals. He is an elected member of the College on Problems of Drug Dependence and the American College of Neuropsychopharmacology. Dr. Kollins is a licensed clinical psychologist and maintains a practice through the ADHD Program’s outpatient clinic. His research interests are in the areas of psychopharmacology and the intersection of ADHD and substance abuse, particularly cigarette smoking.
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