Yonsei Med J.  2017 Jul;58(4):689-696. 10.3349/ymj.2017.58.4.689.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

• Shin MJ
• Cho Y
• Davey Smith G

• KMID: 2419072
• DOI: http://doi.org/10.3349/ymj.2017.58.4.689

Abstract

Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism. Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks. Mendelian randomization (MR) studies have demonstrated that alcohol consumption predicted by ALDH2 genotype is causally related to cardiovascular risks. Moreover, recent MR studies suggest that the ALDH2 variant has mechanistic effects on some disease outcomes or mortality through increased blood levels of acetaldehyde, showing differences therein between heterozygotes (ALDH2*2*2) and homozygotes (ALDH2*1*2) in those who consume alcohol. Accordingly, consideration of ALDH2 genotype in alcohol prevention programs is warranted. In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required.

Keyword

Alcohol; aldehyde dehydrogenase 2; Mendelian randomization analysis; guidelines

MeSH Terms

Alcohol Drinking/epidemiology/*genetics
Aldehyde Dehydrogenase, Mitochondrial/*genetics
Cardiovascular Diseases/*enzymology/*genetics
*Genetic Predisposition to Disease
Humans
Mendelian Randomization Analysis
*Polymorphism, Genetic
Republic of Korea
Aldehyde Dehydrogenase, Mitochondrial

Figure

• 

  Fig. 1 Alcohol metabolism according to genetic polymorphisms. (A) Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) are involved in alcohol metabolism. Generally, ALDH2 variants have a greater influence on alcohol intake than ADH1B variants in East Asians. (B) ALDH2 variants mainly exist in East Asian populations. Adapted from Cho, et al. Sci Rep 2015;5:18422.6

• 

  Fig. 2 Scheme of the Mendelian randomization approach. The scheme of the Mendelian randomization approach. (A) This method uses a genetic variant, which proxies for exposure that is expected to be related to the outcome. (B) Using the Mendelian randomization approach, the causal effects of alcohol intake on cardiovascular outcomes can be investigated while controlling confounders and reverse causation. ALDH2, aldehyde dehydrogenase 2.

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