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

  • Genetics (GVZ Dedoussis, Section Editor)
  • Published:
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Abstract

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.

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Abbreviations

ADH:

Alcohol dehydrogenase

ALDH2:

Aldehyde dehydrogenase 2

ApoC3:

Apolipoprotein C 3

CVD:

Cardiovascular disease

CRP:

C-reactive protein

HDL-C:

High-density lipoprotein cholesterol

sICAM-1:

Soluble intercellular adhesion molecule-1

IL-6:

Interleukin-6

LPL:

Lipoprotein lipase

LDL-C:

Low-density lipoprotein cholesterol

MEOS:

Microsomal ethanol oxidizing system

PON-1:

Paraoxonase-1

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PAI-1:

Plasminogen activator inhibitor-1

SNPs:

Single nucleotide polymorphisms

sVCAM-1:

Soluble vascular cell adhesion molecule-1

tPA:

Tissue plasminogen activator

TNF:

Tumor necrosis factor

and WBC:

White blood cell count

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Acknowledgments

Edmond K. Kabagambe was supported by the National Scientist Development Grant # 0635323N from the American Heart Association.

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Conflict of Interest

James N. Kiage, Laurence O. James, and Edmond K. Kabagambe declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37203, USA

    James N. Kiage, Laurence O. James & Edmond K. Kabagambe

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  1. James N. Kiage
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  2. Laurence O. James
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  3. Edmond K. Kabagambe
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Correspondence to Edmond K. Kabagambe.

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Kiage, J.N., James, L.O. & Kabagambe, E.K. Genetic Modification of the Effects of Alcohol on Metabolic and Clinical Phenotypes: A Review. Curr Nutr Rep 3, 213–222 (2014). https://doi.org/10.1007/s13668-014-0086-2

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