Sarkar DK1, Gangisetty O1, Jabbar S1, Wozniak J2, Boys CJ2, Chambers C3, Wertelecki W3, CIFASD4
1Endocrinology Program and Department of Animal Sciences, Rutgers University, New Brunswick, NJ 08901
2Department of Psychiatry, University of Minnesota, Minneapolis, MN 55454
3Dept. Pediatrics, University of California, San Diego, CA 92093
4Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120
Epigenetic modifications of a gene have been shown to play a role in maintaining long-lasting changes in gene expression. Animal studies have identified epigenetic marks on various genes that alter physiological functions in fetal alcohol exposed animals. These findings led us to hypothesize that alcohol’s modulation of DNA methylation on certain genes could persist in offspring and might serve as biomarkers for maternal alcohol use and outcomes in their offspring. We employed salivary samples from children 7-16 years old with fetal alcohol spectrum disorders (FASD), alcohol exposed but no sign of FASD, and non-alcohol exposed controls from a cross sectional study conducted by CIFASD investigators in the US. We also collected blood samples as part of a longitudinal study conducted by CIFASD investigators at two sites in Ukraine from three groups of mothers: a) women who reported frequent moderate to heavy drinking and had a child with FASD, b) women who reported frequent moderate to heavy drinking and had a child without evidence of FASD, and c) women who reported low or no alcohol consumption in pregnancy. Using state-of-the art epigenetic methods we measured DNA methylation of two stress-axis regulatory genes (proopiomelanocortin, POMC; period 2; PER2) in both salivary and blood DNA samples. We also measured stress hormone levels (cortisol and beta-endorphin) in saliva samples. We found significant increases in methylation of POMC and PER2 genes and elevated levels of cortisol and beta-endorphin in salivary samples of FASD or alcohol-exposed children without FASD as compared to control children. Additionally, we found higher DNA methylation of POMC and PER2 genes in mothers who gave birth to FASD or alcohol exposed children as compared to controls. These results indicate that alcohol epigenetic marks on PER2 and POMC genes might be transmitted from mother to child; hence, PER2 and POMC gene methylation levels in pregnant women could potentially identify children at risk for FASD. (Supported by NIH Grant U24 AA014811, U01 AA014835, NIH ODS).