Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians.
BACKGROUND
Although hypersensitivity reactions following intake of alcoholic drinks are common in Caucasians, the underlying mechanisms and clinical significance are not known. In contrast, in Asians, alcohol-induced asthma and flushing have been shown to be because of a single nucleotide polymorphism (SNP), the acetaldehyde dehydrogenase 2 (ALDH2) 487lys, causing decreased acetaldehyde (the metabolite of ethanol) metabolism and high levels of histamine. However, the ALDH2 487lys is absent in Caucasians.


OBJECTIVE
To investigate the genetic determinants of self-reported alcohol-induced hypersensitivity reactions in Caucasians.


METHODS
The study included two population-based studies of 1216 and 6784 adults living in Copenhagen. Assessment of alcohol consumption and hypersensitivity reactions (in a subgroup) was performed by a questionnaire and was related to common SNPs of genes encoding alcohol dehydrogenases (ADHs) and ALDHs.


RESULTS
In both populations, alcohol drinkers with a genetically determined fast metabolism of ethanol (the A allele of the ADH1b rs1229984) had an increased risk of alcohol-induced hypersensitivity reactions (odds ratio AA/AG vs. GG in combined populations: 1.82, 95% CI 1.04-3.17). In both populations, a common SNP encoding ALDH1b1 (rs2228093) was found to be significantly associated with alcohol-induced hypersensitivity (odds ratio TT vs. CC in combined populations: 2.53, 95% CI 1.31-4.90).


CONCLUSIONS
Our data support that alcohol sensitivity in Caucasians is genetically determined and suggest that a histamine-releasing effect of acetaldehyde represents a plausible biological mechanism. Furthermore, we present the first report of a clinically significant SNP within the acetaldehyde-metabolizing system in a Caucasian population.
Linneberg
A
A
Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark. alli@glo.regionh.dk
Gonzalez-Quintela
A
A
Vidal
C
C
Jørgensen
T
T
Fenger
M
M
Hansen
T
T
Pedersen
O
O
Husemoen
L L N
LL
D000079:Acetaldehyde / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000434:Alcoholic Beverages / Q000009:adverse effects*; D000437:Alcoholism / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D003718:Denmark; D004342:Drug Hypersensitivity / Q000235:genetics*; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D044465:White People
D000431:Ethanol; D000080924:Aldehyde Dehydrogenase 1 Family; C524846:ALDH1B1 protein, human; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde