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Research ArticleArticle

Effects of Aldehyde Dehydrogenase-2 Genetic Polymorphisms on Metabolism of Structurally Different Aldehydes in Human Liver

Rui-Sheng Wang, Tamie Nakajima, Toshihiro Kawamoto and Takeshi Honma
Drug Metabolism and Disposition January 2002, 30 (1) 69-73; DOI: https://doi.org/10.1124/dmd.30.1.69
Rui-Sheng Wang
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Tamie Nakajima
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Toshihiro Kawamoto
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Takeshi Honma
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Abstract

Genotype analysis of the aldehyde dehydrogenase (ALDH)-2 gene was performed using an improved simplified method, and effects of the genotype on the metabolism of a variety of aldehydes in different fractions of human liver cells were investigated. The effects of sex, aging, smoking, drinking alcohol, liver function, and various drugs on ALDH activity were also analyzed. Of the 39 subjects, eight were heterozygotes of the wild (ALDH2*1) and mutant (ALDH2*2) alleles, and the others were homozygotes of the wild allele. ALDH activity toward acetaldehyde in liver mitochondria from subjects with a mutant allele was less than 10% of that with two alleles of wild-type, and the activities toward formaldehyde, propionaldehyde,n-butyraldehyde, capronaldehyde, and heptaldehyde were also significantly lower in the ALDH2*1/*2 rather than ALDH2*1/*1 group. However, the metabolism of octylaldehyde, decylaldehyde, retinaldehyde, benzaldehyde, 3-hydroxybenzaldehyde, and 2,5-dihydroxybenzaldehyde was similar in the two genotypes. Changes in activity in the cytosolic fraction were similar to those in mitochondria. There was no significant difference in ALDH activity in microsomes between the two groups. Total activities of ALDH toward acetaldehyde and other short-chain aliphatic aldehydes in supernatant fractions of homogenized liver were affected in a manner similar to that in mitochondria. Our results suggest that the single nucleotide polymorphisms of the ALDH2 gene only alter the metabolism of aldehydes with a short aliphatic chain. Furthermore, sex, drinking alcohol, and smoking had little effect on ALDH activity, although the activity in elderly individuals tended to be lower albeit statistically insignificant.

Footnotes

  • Abbreviations used are::
    ALDH
    aldehyde dehydrogenase
    SNPs
    single nucleotide polymorphisms
    PCR
    polymerase chain reaction
    bp
    base pair
    • Received April 24, 2001.
    • Accepted October 5, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 30 (1)
Drug Metabolism and Disposition
Vol. 30, Issue 1
1 Jan 2002
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Research ArticleArticle

Effects of Aldehyde Dehydrogenase-2 Genetic Polymorphisms on Metabolism of Structurally Different Aldehydes in Human Liver

Rui-Sheng Wang, Tamie Nakajima, Toshihiro Kawamoto and Takeshi Honma
Drug Metabolism and Disposition January 1, 2002, 30 (1) 69-73; DOI: https://doi.org/10.1124/dmd.30.1.69

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Research ArticleArticle

Effects of Aldehyde Dehydrogenase-2 Genetic Polymorphisms on Metabolism of Structurally Different Aldehydes in Human Liver

Rui-Sheng Wang, Tamie Nakajima, Toshihiro Kawamoto and Takeshi Honma
Drug Metabolism and Disposition January 1, 2002, 30 (1) 69-73; DOI: https://doi.org/10.1124/dmd.30.1.69
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