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Human Molecular Genetics Advance Access published online on October 6, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm295
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

ASSOCIATION OF THE GASTRIC ALCOHOL DEHYDROGENASE GENE ADH7 WITH VARIATION IN ALCOHOL METABOLISM

Andrew J Birley1,{ddagger}, Michael R James1,{ddagger}, Peter A Dickson1,§, Grant W Montgomery1, Andrew C Heath2, John B Whitfield1 and Nicholas G Martin1,*

1 Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia 2 Midwest Alcoholism Research Center, Washington University, St Louis MO

* Author for correspondence. Dr Nick Martin, Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia. Phone (+61) 7 3362 0278, Fax (+61) 7 3362 0101, email Nick.Martin{at}qimr.edu.au

Received October 1, 2007; Revised October 3, 2007; Accepted October 3, 2007

Seven alcohol metabolising enzymes are encoded by the human alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence metabolism of alcohol before its absorption into the blood. However, the contribution of ADH7to the overall genetic variation in alcohol oxidation in vivo is unknown. Data on in vivo alcohol metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75g. kg–1body weight) of alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped. The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of alcohol metabolism. These are within a 35kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene. The region accounts for 18% of the linkage for alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.

{ddagger} These authors contributed equally to this work.

§ Peter Dickson died on 15th October 2005


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A. J. Birley, M. R. James, P. A. Dickson, G. W. Montgomery, A. C. Heath, N. G. Martin, and J. B. Whitfield
ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Hum. Mol. Genet., April 15, 2009; 18(8): 1533 - 1542.
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