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Environmental Health and Preventive Medicine

, Volume 21, Issue 6, pp 395–402 | Cite as

Roles of defective ALDH2 polymorphism on liver protection and cancer development

  • Akiko Matsumoto
  • David C. Thompson
  • Ying Chen
  • Kyoko Kitagawa
  • Vasilis Vasiliou
Review

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.

Keywords

ALDH2 Gene polymorphism Serum transaminase Alcohol Cancer 

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

Notes

Acknowledgments

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

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© The Japanese Society for Hygiene 2016

Authors and Affiliations

  • Akiko Matsumoto
    • 1
  • David C. Thompson
    • 2
  • Ying Chen
    • 3
  • Kyoko Kitagawa
    • 4
  • Vasilis Vasiliou
    • 3
  1. 1.Department of Social MedicineSaga University School of MedicineSagaJapan
  2. 2.Department of Clinical PharmacyUniversity of Colorado School of PharmacyDenverUSA
  3. 3.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA
  4. 4.Department of Molecular BiologyHamamatsu University School of MedicineHamamatsuJapan

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