Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene expression

Howard Edenberg, Ronald E. Jerome, Mei Li

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The human alcohol dehydrogenase 4 gene (ADH4) encodes the human π-alcohol dehydrogenase (π-ADH), which can contribute to ethanol metabolism at moderate and high concentrations of ethanol. There are no known structural variants of π-ADH in humans. We report the first polymorphisms in the ADH4 gene, at three sites in the promoter: -192 bp, -159 bp and -75 bp, respectively. To determine whether these variations affected promoter function, different haplotypes of the ADH4 proximal promoter were subcloned into a luciferase reporter vector, and the relative promoter activity analysed in hepatoma cells. One of the three sites had a dramatic effect on promoter activity while the others did not detectably affect activity. The -75A allele had promoter activity more than twice that of the -75C allele. Alcohol dehydrogenase activity is rate limiting for ethanol oxidation. We hypothesize that the different ADH4 alleles lead to different amounts of π-ADH in liver, which affects the risk for alcoholism by modulating alcohol metabolism.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalPharmacogenetics
Volume9
Issue number1
StatePublished - 1999

Fingerprint

Gene Expression
Ethanol
Alcohol Dehydrogenase
Alleles
Luciferases
Haplotypes
Alcoholism
Genes
Hepatocellular Carcinoma
Alcohols
alcohol dehydrogenase IV
Liver

Keywords

  • Alcohol metabolism
  • Alcoholism
  • Functional polymorphism
  • Gene expression
  • Human genetics
  • Promotor function

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene expression. / Edenberg, Howard; Jerome, Ronald E.; Li, Mei.

In: Pharmacogenetics, Vol. 9, No. 1, 1999, p. 25-30.

Research output: Contribution to journalArticle

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