From genes to therapy: A study on how genetics can help identifying novel targets for alcohol dependence

Abstract

Alcohol addiction is a major public health burden. Treatment strategies available for alcoholism are limited in number and efficacy. This current review is focused on how genetic studies can contribute and have contributed to finding novel workable therapies for alcoholism. I address five candidate genes with strong evidence for associations with alcohol dependence: two ethanol-metabolizing genes (alcohol dehydrogenase enzyme, ADH1B, and aldehyde dehydrogenase enzyme ALDH2), one opioid receptor gene (OPRM1), one dopamine receptor gene (DRD2), and one GABA receptor gene (GABRA2). These genes show strong associations with alcohol dependence. Some functional polymorphisms predispose an individual for developing alcohol dependence, like those in the DRD2 receptor. In contrast, variants of the ADH1B and the ALDH2 genes are believed to have a protective effect, since the ethanol-metabolizing process is altered such that accumulated acetaldehyde leads to strong intoxication responses shortly after drinking alcohol (alcohol-induced flushing trait). One candidate gene displays qualities that allow patient-tailored treatment based on their individual’s genotype. The Asp40 variant allele of the OPRM1 gene improves the receptor ability such that treatment with naltrexone is more efficient, thus giving a subgroup of alcoholics a better chance of withstanding relapse. Despite discovering haplotypes on the DRD2 and GABR2 genes associating the dopaminergic and GABAergic system to alcoholism, drug treatments almost always lead to side-effects because of the complexity of these pathways. Further research is required. I feel that genetic studies can contribute profoundly to developing drug treatments. With pharmacogenetic studies, it may be possible in the future to develop personalized drug treatments for alcoholism by making use of information on the genotype and the genetic predisposition (the contribution of genetic versus environment) related to the expected response to drug treatment.