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Hypermethylation of Proopiomelanocortin and Period 2 Genes in Blood Are Associated with Greater Subjective and Behavioral Motivation for Alcohol in Humans
Author(s) -
Gangisetty Omkaram,
Sinha Rajita,
Sarkar Dipak K.
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13932
Subject(s) - dna methylation , binge drinking , epigenetics , alcohol , craving , proopiomelanocortin , methylation , psychology , alcohol intoxication , gene expression , gene , medicine , genetics , poison control , biology , addiction , alcohol consumption , psychiatry , injury prevention , biochemistry , environmental health
Background Epigenetic modifications of a gene have been shown to play a role in maintaining a long‐lasting change in gene expression. We hypothesize that alcohol's modulating effect on DNA methylation on certain genes in blood is evident in binge and heavy alcohol drinkers and is associated with alcohol motivation. Methods Methylation‐specific polymerase chain reaction (PCR) assays were used to measure changes in gene methylation of period 2 ( PER 2) and proopiomelanocortin ( POMC ) genes in peripheral blood samples collected from nonsmoking moderate, nonbinging, binge, and heavy social drinkers who participated in a 3‐day behavioral alcohol motivation experiment of imagery exposure to either stress, neutral, or alcohol‐related cues, 1 per day, presented on consecutive days in counterbalanced order. Following imagery exposure on each day, subjects were exposed to discrete alcoholic beer cues followed by an alcohol taste test ( ATT ) to assess behavioral motivation. Quantitative real‐time PCR was used to measure gene expression of PER 2 and POMC gene levels in blood samples across samples. Results In the sample of moderate, binge, and heavy drinkers, we found increased methylation of the PER 2 and POMC DNA , reduced expression of these genes in the blood samples of the binge and heavy drinkers relative to the moderate, nonbinge drinkers. Increased PER 2 and POMC DNA methylation was also significantly predictive of both increased levels of subjective alcohol craving immediately following imagery ( p < 0.0001), and with presentation of the alcohol (2 beers) ( p < 0.0001) prior to the ATT , as well as with alcohol amount consumed during the ATT ( p < 0.003). Conclusions These data establish significant association between binge or heavy levels of alcohol drinking and elevated levels of methylation and reduced levels of expression of POMC and PER 2 genes. Furthermore, elevated methylation of POMC and PER 2 genes is associated with greater subjective and behavioral motivation for alcohol.