Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol

Dipak K. Sarkar, Omkaram Gangisetty, Jeffrey R. Wozniak, Judith K. Eckerle, Michael K. Georgieff, Tatiana M. Foroud, Leah Wetherill, Wladimir Wertelecki, Christina D. Chambers, Edward Riley, Natalya Zymak-Zakutnya, Lyubov Yevtushok

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: We have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis. Methods: We conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate-to-high levels of alcohol or low/unexposed controls, (ii) children with PAE and non–alcohol-exposed controls, and (iii) children with PAE treated with or without choline. Results: We found pregnant women who consumed moderate-to-high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE. Conclusions: These data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.

Original languageEnglish (US)
Pages (from-to)1887-1897
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Issue number9
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
The authors thank Shaima Jabbar for technical assistance in the ELISA assays for stress hormones. This work was supported by National Institutes of Health Grants U24 AA014811, U01 AA014835, U01AA014809, R21AA019580, R33AA019580. We are grateful to the OMNI-Net Birth Defects Prevention Program and to the women and their children who participated in this study. We also acknowledge the CIFASD ( for intellectual and administrative support.

Publisher Copyright:
© 2019 by the Research Society on Alcoholism


  • Circadian
  • DNA Methylation
  • FASD
  • Gene Expression
  • Stress Axis


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