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Human Molecular Genetics Advance Access originally published online on February 4, 2009
Human Molecular Genetics 2009 18(8):1533-1542; doi:10.1093/hmg/ddp060
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

ADH single nucleotide polymorphism associations with alcohol metabolism in vivo

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

1 Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia 2 Midwest Alcoholism Research Center, Washington University, St Louis, MO, USA

* To whom correspondence should be addressed. Tel: +61 7 3362 0229; Fax: +61 7 3362 0101; Email: John.Whitfield{at}qimr.edu.au

Received December 4, 2008; Accepted February 2, 2009

We have previously found that variation in alcohol metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath alcohol concentrations after an alcohol challenge. In vivo alcohol metabolism was modelled with three parameters that identified the absorption and rise of alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting alcohol metabolism did not correspond to those reported to affect alcohol dependence or alcohol-related disease. The combined SNP associations with early- and late-stage metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo alcohol metabolism linked to this region is yet to be explained.

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

{ddagger} Peter Dickson died on 15 October 2005.


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