Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians

TY - JOUR

T1 - Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians

AU - Linneberg, A

AU - Gonzalez-Quintela, A

AU - Vidal, C

AU - Jørgensen, Torben

AU - Fenger, M

AU - Hansen, T

AU - Pedersen, Oluf

AU - Husemoen, L L N

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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. Objectives 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.

AB - 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. Objectives 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.

KW - Acetaldehyde

KW - Adolescent

KW - Adult

KW - Aged

KW - Alcoholic Beverages

KW - Alcoholism

KW - Aldehyde Dehydrogenase

KW - Alleles

KW - Denmark

KW - Drug Hypersensitivity

KW - Ethanol

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Middle Aged

U2 - 10.1111/j.1365-2222.2009.03398.x

DO - 10.1111/j.1365-2222.2009.03398.x

M3 - Journal article

C2 - 20205700

SN - 0954-7894

VL - 40

SP - 123

EP - 130

JO - Clinical Allergy

JF - Clinical Allergy

IS - 1

ER -