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Roles of defective ALDH2 polymorphism on liver protection and cancer development

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Environmental Health and Preventive Medicine Aims and scope

Abstract

Because serum transaminases elevate alcohol dose dependently as a consequence of liver injury, they serve as useful biological markers of excessive drinking. However, these markers are inadequate in individuals with a defective allele of the aldehyde dehydrogenase 2 gene, ALDH2*2, because they show a different correlation with the amount of ethanol. For example, the serum alanine aminotransferase (ALT) level could become even lower than the baseline after alcohol intake in ALDH2*2 carriers. In fact, multiple studies suggest that ALDH2*2 is a hepato-protective factor in healthy individuals. Importantly, excessive drinking is particularly dangerous in carriers of ALDH2*2 because the risk of alcohol-related cancer is much higher than that for ALDH2*1/*1 carriers. Without recognizing the genotype interaction on serum transaminase, the opportunity to warn people about potential cancer risks is missed owing to incorrect interpretation. This is particularly important in East Asian countries where approximately half of the population carries the ALDH2*2 allele. To date, the mechanism of liver protection from ethanol load in individuals with ALDH2*2 has not been fully elucidated. However, some reasonable mechanisms have been suggested by experimental studies, including remodelling of detoxifying systems. Further studies to uncover the whole mechanism are anticipated.

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Abbreviations

ALDH2:

Aldehyde dehydrogenase 2

AST:

Aspartate aminotransferase

ALT:

Alanine transaminase

GGT:

Gamma-glutamyltransferase

4HNE:

4-hydroxy-2-nonenal

MDA:

Malondialdehyde

SNPs:

Single nucleotide polymorphisms

TNFα:

Tumour necrosis factor-alpha

GSH:

Glutathione

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Acknowledgments

This work was supported by JSPS Grant-in-Aid for Young Scientists (B) Grant Number 25870515.

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Authors and Affiliations

  1. Department of Social Medicine, Saga University School of Medicine, Saga, 849-8501, Japan

    Akiko Matsumoto

  2. Department of Clinical Pharmacy, University of Colorado School of Pharmacy, 12850 E. Aurora, Denver, CO, 80045, USA

    David C. Thompson

  3. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06520-8034, USA

    Ying Chen & Vasilis Vasiliou

  4. Department of Molecular Biology, Hamamatsu University School of Medicine, Hamamatsu, 431-3125, Japan

    Kyoko Kitagawa

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  1. Akiko Matsumoto
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Correspondence to Akiko Matsumoto.

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Matsumoto, A., Thompson, D.C., Chen, Y. et al. Roles of defective ALDH2 polymorphism on liver protection and cancer development. Environ Health Prev Med 21, 395–402 (2016). https://doi.org/10.1007/s12199-016-0579-2

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