Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression.
- Authors
- Chen, Hui-Ju; Tian, Huijun; Edenberg, Howard J
- Year
- 2005
- Journal
- Human mutation
- PMID
- 15643610
- DOI
- 10.1002/humu.20127
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.
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In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. | Edenberg HJ et al. | — | 2018 | → |
| Alcohol metabolism and oesophageal cancer: a systematic review of the evidence. | Matejcic M et al. | — | 2017 | → |
| Associations Between Genomic Variants in Alcohol Dehydrogenase Genes and Alcohol Symptomatology in American Indians and European Americans: Distinctions and Convergence. | Peng Q et al. | — | 2017 | → |
| Novel polymorphisms in the promoter region of the perforin gene among distinct Brazilian populations and their functional impact. | Garcia FB et al. | — | 2014 | → |
| Genes encoding enzymes involved in ethanol metabolism. | Hurley TD et al. | — | 2012 | → |
| Variation in the ADH1B proximal promoter affects expression. | Pochareddy S et al. | — | 2011 | → |
| Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a prospective follow-up study. | Kesmodel US et al. | — | 2010 | → |
| The genetic factors affecting drinking behaviors of korean young adults with variant aldehyde dehydrogenase 2 genotype. | Kim SK et al. | — | 2010 | → |
| ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. | Birley AJ et al. | — | 2009 | → |
| Regulatory polymorphisms and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition. | Hines RN et al. | — | 2008 | → |
| The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. | Edenberg HJ | — | 2007 | → |