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

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2019-09, Vol.43 (9), p.1887-1897
• Main Authors: Sarkar, Dipak K., Gangisetty, Omkaram, Wozniak, Jeffrey R., Eckerle, Judith K., Georgieff, Michael K., Foroud, Tatiana M., Wetherill, Leah, Wertelecki, Wladimir, Chambers, Christina D., Riley, Edward, Zymak‐Zakutnya, Natalya, Yevtushok, Lyubov
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenocorticotropic hormone; Adult; Alcohol; Alcohol use; Alcohols; Biological properties; Biological samples; Case-Control Studies; Central Nervous System Depressants - adverse effects; Child; Child, Preschool; Children; Choline; Choline - pharmacology; Choline - therapeutic use; Circadian; Cortisol; Deoxyribonucleic acid; Dietary Supplements; DNA; DNA Methylation; DNA Methylation - drug effects; Drinking behavior; Epigenesis, Genetic - drug effects; Ethanol - adverse effects; Exposure; FASD; Female; Fetal Alcohol Spectrum Disorders - metabolism; Fetal Alcohol Spectrum Disorders - prevention & control; Gene Expression; Gene Expression Regulation - drug effects; Humans; Hypotheses; Lipotropic Agents - pharmacology; Lipotropic Agents - therapeutic use; Male; Menopause; Period 2 protein; Period Circadian Proteins - metabolism; Pregnancy; Prenatal experience; Prenatal Exposure Delayed Effects; Pro-Opiomelanocortin - metabolism; Proopiomelanocortin; Smoking; Stress; Stress Axis; Supplements; Women; Womens health
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14148

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. Sarkar and his colleagues found pregnant women who consumed moderate‐to‐high levels of alcohol and gave birth to prenatal alcohol exposed children had higher DNA methylation of PER2, which influences the body's biological clock, and POMC, which regulates our stress‐response system. Prenatal alcohol exposed children also had increased methylation of POMC and PER2. The authors proposed that DNA methylation changes in PER2 and POMC could be used as biomarkers to predict risk of prenatal alcohol exposure.