Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity, consumption, and dependence in Europeans.
BACKGROUND
The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry.


METHODS
Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects.


RESULTS
The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations.


CONCLUSIONS
Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence.
Dickson
Peter A
PA
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
James
Michael R
MR
Heath
Andrew C
AC
Montgomery
Grant W
GW
Martin
Nicholas G
NG
Whitfield
John B
JB
Birley
Andrew J
AJ
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D000435:Alcoholic Intoxication / Q000097:blood / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001794:Blood Pressure / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006239:Haplotypes; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D004856:Postural Balance / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects; D044465:White People / Q000235:genetics
D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial