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PMID: 18996923 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Twin Study

Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.

Human molecular genetics ·Vol. 18 ·No. 3 ·2009-02-01 ·Pages 580-93

Macgregor S, Lind PA, Bucholz KK, Hansell NK, Madden PA, Richter MM, Montgomery GW, Martin NG, Heath AC, Whitfield JB

Abstract

Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P<2.3 x 10(-4)) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P<0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P=8.2 x 10(-7)), consumed alcohol on more occasions (P=2.7 x 10(-6)), had a higher maximum number of alcoholic drinks in a single day (P=2.7 x 10(-6)) and a higher overall alcohol consumption (P=8.9 x 10(-8)) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P=4.7 x 10(-5)) and suggestive associations (P<0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes.

MeSH Terms
Adult Aged Aged, 80 and over Alcohol Dehydrogenase/genetics,metabolism Alcohol Drinking Alcoholism/genetics,metabolism,psychology Aldehyde Dehydrogenase/genetics,metabolism Aldehyde Dehydrogenase, Mitochondrial Australia Diseases in Twins/genetics Female Flushing/genetics,metabolism Genetic Variation Humans Male Middle Aged Polymorphism, Single Nucleotide Whites/genetics
Chemicals
ADH1B protein, human Alcohol Dehydrogenase ALDH2 protein, human Aldehyde Dehydrogenase Aldehyde Dehydrogenase, Mitochondrial
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Macgregor Stuart
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. [email protected]
Lind Penelope A
Bucholz Kathleen K
Hansell Narelle K
Madden Pamela A F
Richter Melinda M
Montgomery Grant W
Martin Nicholas G
Heath Andrew C
Whitfield John B
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Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
1460-2083
DOI
10.1093/hmg/ddn372
Email
[email protected]
Published
2009-02-01
Epub
2008-00-07
Pages
580-93
Language
English
Region
England
NLM ID
9208958
PMCID
PMC2722191
Subset
IM
Grants
NIAAA NIH HHS · AA13320 · United States
NIAAA NIH HHS · AA13321 · United States
NIAAA NIH HHS · AA013326 · United States
NIAAA NIH HHS · AA07728 · United States
NIAAA NIH HHS · AA11998 · United States
NIAAA NIH HHS · AA014041 · United States
NIAAA NIH HHS · AA07535 · United States
External Links
PubMed source DOI: 10.1093/hmg/ddn372 PMC Full Text View journal details
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