Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression

Hui Ju Chen, Huijun Tian, Howard Edenberg

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human alcohol dehydrogenases (ADHs) play important roles in metabolizing alcohol, and several lines of evidence suggest that variations in ADH genes affect the risk for alcoholism. Differences in regulatory sequences could affect the expression of ADH genes and thereby modify the risk for alcoholism. To explore this idea, we sequenced regulatory regions upstream of ADH1C and identified 13 polymorphisms, including one 66-base pair (bp) insertion/deletion (in/del), one 5-bp variation, and 11 single nucleotide polymorphisms (SNPs), eight of which were newly identified. We examined the effects of naturally occurring haplotypes on gene expression. The 66-bp in/del alone did not change promoter activity, but when it was combined with three other SNP alleles, a twofold difference in transcription activity was observed in transient transfection assays in H4IIE-C3 cells. These data imply that there are interactions among polymorphisms in the cis-acting elements, and highlight the importance of studying regulatory polymorphisms within the context of their naturally occurring haplotypes. We also demonstrated tissue specificity in cis-acting elements by comparing gene expression in H4IIE-C3 and HeLa cells.

Original languageEnglish
Pages (from-to)150-155
Number of pages6
JournalHuman Mutation
Volume25
Issue number2
DOIs
StatePublished - 2005

Fingerprint

Alcohol Dehydrogenase
Haplotypes
Base Pairing
Gene Expression
Alcoholism
Single Nucleotide Polymorphism
Organ Specificity
Nucleic Acid Regulatory Sequences
HeLa Cells
Genes
Transfection
Alleles
Alcohols

Keywords

  • ADH1C
  • Alcohol dehydrogenase
  • Cis-acting element
  • Gene regulation
  • Haplotype
  • SNP
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression. / Chen, Hui Ju; Tian, Huijun; Edenberg, Howard.

In: Human Mutation, Vol. 25, No. 2, 2005, p. 150-155.

Research output: Contribution to journalArticle

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