, Volume 3, Issue 3, pp 213-222
Date: 03 Jun 2014

Genetic Modification of the Effects of Alcohol on Metabolic and Clinical Phenotypes: A Review


Moderate alcohol intake is associated with improved high-density lipoprotein cholesterol, inflammation, insulin sensitivity and a lower risk of cardiovascular disease. These beneficial effects have not been consistent across studies. Genetic mechanisms that regulate alcohol intake and metabolism may in part explain the inconsistencies. In this report we review evidence of the impact of genetic variation on the effects of moderate alcohol intake on metabolic and clinical phenotypes. We focused on single nucleotide polymorphisms in major alcohol-metabolizing enzyme genes, particularly alcohol dehydrogenases (i.e., ADH1B, ADH1C and ADH7), aldehyde dehydrogenase, and cytochrome P450 2E1 because of their reported effects on gene transcription rates, enzyme activity and association with clinical endpoints. We report that while there is evidence for genetic modification of the effects of alcohol on various metabolic phenotypes, most studies are based on minimally genotyped populations. Studies using dense markers (e.g., from exome sequencing) are needed and may explain some of the inconsistencies.