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Monday, December 22, 2008

Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis
Human Molecular Genetics Advance Access published online on November 7, 2008


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 DSMIIIR criteria for AD.
There were study-wide significant associations (p<2.3x10–4) p="8.2x10–7)," p="2.7x10–6)," p="2.7x10–6)" p="8.9x10–8)">
After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (p=4.7x10–5) and suggestive associations (p<0.001)>
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 alcohol dependence results from the low p-value required when testing multiple SNPs and phenotypes.
Request Reprint E-Mail: stuart.macgregor@qimr.edu.au
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