The study of DNA methylation as an important epigenetic pathway may reveal possible effects of alcohol exposure on the alcoholic's DNA methylation profile that probably result in the transmission of altered or imprinted patterns of gene expression to offspring and subsequent predisposition to alcohol related behaviors. The proposed project aims to determine the effects of chronic ethanol exposure on gene methylation patterns, whether changes in DNA methylation are transmitted to offspring and whether such changes correlate with alcoholism related behavioral changes. Behavior of male offspring of chronic ethanol treated and control male rats will be analyzed and high throughput microarrays will be used to identify differentially methylated gene promoter regions within the genome of this offspring. Genes that show differentially methylated patterns between the offspring of ethanol treated and control rats will be analyzed for methylation changes of specific CpG sites in both parents and offspring to analyze heritability. If epigenetic changes precede addiction and confer risk for dependence, that would be a strong argument for causality. These scientific aims are closely coordinated with the training aspects of the project which emphasize development of expertise in rat behavior genetics and epigenetics. Together, the research and training components of the proposed project will provide the applicant with the foundation to pursue research on epigenetic factors and investigate their role in alcohol abuse in human subjects by using animal models. Candidate's long-term goal is to develop a research program that combines rodent and human behavior genetics, including the extent and importance of epigenetic variations and mechanisms by which dynamic and quantitative aspects of alcohol dependent behavior are controlled.
This project is relevant to public health, as new strategies (microarray-based epigenetic profiling followed by specific gene methylation analysis) can be used for testing the epigenetic effects in alcohol behavior in rodents and humans. It will lead to investigations that may advance knowledge in the areas of epigenetics, GxE interaction, treatment, and prevention of alcohol abuse. Health care can then be redirected from curative to individualized preventive medicine based on epigenetic characteristics of one's genetic makeup.
|Chorbov, Vesselin M; Todorov, Alexandre A; Lynskey, Michael T et al. (2011) Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts. J Opioid Manag 7:258-64|