Identifying Susceptibility Genes and Epigenetic Mechanisms for Drugs of Abuse

November 30, 2015
Identifying Susceptibility Genes and Epigenetic Mechanisms for Drugs of Abuse
Source: DepositPhotos/agsandrew

Patricia Fitzpatrick Dimond, Ph.D.

As researchers continue to find numerous genes that may increase the risk for drug and alcohol dependence, a complex and multifactorial picture continues to emerge. Genetic differences in individual physiology, drug- or alcohol-induced changes in epigenetic gene regulation and expression, and developmental and environmental factors all contribute to the development and persistence of chronic substance abuse. All evidence indicates that save for a very few well-validated genetic variations, reliable screening for substance dependence that identifies at-risk individuals remains a long way off.

Twin and adoption studies have confirmed that genes contribute to the development of alcohol dependence (AD) with heritability estimates ranging from 50–60% for both men and women. Studies examining drug dependence among twins suggested that among identical twins, shared genes influence the risk of both alcohol and drug dependence.

For alcoholism, the most significant and durable identifiable genetic risk factors involve genes linked to ethanol metabolism. Genetic variations in enzymes, such as variants of the alcohol dehydrogenase (ALDH) gene, allow buildup of the toxic metabolite acetaldehyde, producing the unpleasant effects associated with hangovers. Among the 40% of Asian Individuals bearing the ALDH2-2 mutation, homozygous individuals experience severe nausea and vomiting and an intense skin flush with low alcohol consumption, reducing the risk of alcohol abuse to almost zero. Heterozygous individuals with one copy of the mutated gene experience more minor symptoms such as skin flush.

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