title: Genetic differences in response to alcohol.
abstract: The level of response to alcohol, which reflects individual differences in sensitivity to the pharmacologic effects of alcohol, is considered to be an important endophenotype of alcohol use disorder (AUD). By comparing monozygotic and dizygotic twins, the heritability of the level of response to alcohol has been estimated to be 60%. Many genes have been implicated as potential contributors toward heavy drinking, alcohol-related problems, and AUD through a low level of response to alcohol, each with a small effect. Identified are genes for gamma-aminobutyric acid (GABA) receptors, serotonin transporter, opioid receptor, and nicotinic acetylcholine receptor, but the most well-characterized genes that have a strong impact on the level of response to alcohol are those for alcohol-metabolizing enzymes. Although two genetic variations in alcohol and aldehyde dehydrogenases, which have been the most intensively studied, exist almost exclusively in Asian populations, studies on the effect of genetic variations in alcohol-metabolizing enzymes on the response to alcohol are gradually expanding in non-Asian populations. In this chapter, we focus on genetic studies in humans. After analyzing the overall influence of genetic factors on the response to alcohol, we explore individual genes that may influence the response to alcohol. Lastly, we review studies examining the effects of genetic variations in alcohol-metabolizing enzymes on the level of response to alcohol.
authors.affiliation: National Hospital Organization, Kurihama Medical and Addiction Center, Kanagawa, Japan. Electronic address: sachio-m@wa2.so-net.ne.jp.
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: National Hospital Organization, Kurihama Medical and Addiction Center, Kanagawa, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics* / Q000473:pathology; D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D011963:Receptors, GABA-A / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000235:genetics
chemical_list: C484841:GABRA2 protein, human; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase
keywords: GABA receptors; alcohol use disorder; alcohol-metabolizing enzymes; genetic factors; nicotinic acetylcholine receptor; opioid receptor; response to alcohol; serotonin transporter