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Environ Health Prev Med. 2016 Nov;21(6):395-402. Epub 2016 Oct 6.

Roles of defective ALDH2 polymorphism on liver protection and cancer development.

Author information

1
Department of Social Medicine, Saga University School of Medicine, Saga, 849-8501, Japan. matsumoa@cc.saga-u.ac.jp.
2
Department of Clinical Pharmacy, University of Colorado School of Pharmacy, 12850 E. Aurora, Denver, CO, 80045, USA.
3
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06520-8034, USA.
4
Department of Molecular Biology, Hamamatsu University School of Medicine, Hamamatsu, 431-3125, Japan.

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; Alcohol; Cancer; Gene polymorphism; Serum transaminase

PMID:
27714678
PMCID:
PMC5112207
[Available on 2017-11-01]
DOI:
10.1007/s12199-016-0579-2
[Indexed for MEDLINE]
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