Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population.
BACKGROUND
Genetic variation in the alcohol dehydrogenase (ADH) enzyme is associated with an aversion to alcohol and a lower risk of alcoholism among Asians. There is growing evidence of a functional role of the ADH2*2 allele in alcohol-drinking patterns among Jews, who have traditionally exhibited low rates of alcoholism and alcohol-related problems. The mechanism by which this allelic effect is mediated is not yet clearly understood. This study examined the effect of ADH2*2 on alcohol-elimination rates (AER) under experimental conditions.


METHODS
Young adult male Jews (N = 109) received an intravenous alcohol infusion; metabolism was measured by using standard breath alcohol concentration tests. A clamping technique was used to achieve and maintain a target breath alcohol concentration of 50 mg/100 ml for a defined time period. The AER at steady state was calculated. The alcohol disappearance rate was also calculated from the descending limb slope. Polymerase chain reaction was used for allelic determination of the ADH2 and ADH3 loci.


RESULTS
The mean AER among ADH2*2 carriers was significantly higher (8.09 +/- 1.4 g/hr) than among ADH2*1 homozygotes (7.14 +/- 1.5 g/hr; p = 0.003). Significance was retained on adjustment for potential confounding covariates. The ADH2 allele explains 8.5% of the AER variance in this population. Little AER difference was observed across ADH3 genotype groups. The slope of the descending limb increased with increasing copies of the ADH2*2 allele.


CONCLUSIONS
The rate of alcohol elimination is significantly associated with the ADH2 genotype of Jewish males. Evidence for variation in alcohol metabolism across ADH genotypic groups provides support for the role of physiologic protective factors in alcohol drinking and suggests that reduced drinking among Jews may be genetically as well as environmentally determined. We believe that application of the novel "Indiana clamp" enhances AER measurement accuracy, allowing for detection of hitherto undetectable differences.
Neumark
Yehuda D
YD
Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem-Hadassah, Jerusalem, Israel. yneumark@md2.huji.ac.il
Friedlander
Yechiel
Y
Durst
Ronen
R
Leitersdorf
Eran
E
Jaffe
Dena
D
Ramchandani
Vijay A
VA
O'Connor
Sean
S
Carr
Lucinda G
LG
Li
T K
TK
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D000704:Analysis of Variance; D001944:Breath Tests / Q000379:methods; D000431:Ethanol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005787:Gene Frequency / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*
D000431:Ethanol; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase