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

A Linneberg, A Gonzalez-Quintela, C Vidal, T Jørgensen, M Fenger, Torben Hansen, O Pedersen, L L N Husemoen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2010-Jan
OriginalsprogEngelsk
TidsskriftClinical and Experimental Allergy
Vol/bind40
Udgave nummer1
Sider (fra-til)123-30
Antal sider7
ISSN0954-7894
DOI
StatusUdgivet - 1. jan. 2010

Fingeraftryk

Drinking Behavior
Acetaldehyde
Alcohol Drinking
Hypersensitivity
Ethanol
Alcohols
Single Nucleotide Polymorphism
Population
Odds Ratio
Histamine Agents
Alcohol Dehydrogenase
Alleles

Citer dette

Linneberg, A ; Gonzalez-Quintela, A ; Vidal, C ; Jørgensen, T ; Fenger, M ; Hansen, Torben ; Pedersen, O ; Husemoen, L L N. / Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians. I: Clinical and Experimental Allergy. 2010 ; Bind 40, Nr. 1. s. 123-30.
@article{b1da26f0aa9411dfb62d000ea68e967b,
title = "Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians",
abstract = "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.",
keywords = "Acetaldehyde, Adolescent, Adult, Aged, Alcoholic Beverages, Alcoholism, Aldehyde Dehydrogenase, Alleles, Denmark, Drug Hypersensitivity, Ethanol, European Continental Ancestry Group, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged",
author = "A Linneberg and A Gonzalez-Quintela and C Vidal and T J{\o}rgensen and M Fenger and Torben Hansen and O Pedersen and Husemoen, {L L N}",
year = "2010",
month = "1",
day = "1",
doi = "10.1111/j.1365-2222.2009.03398.x",
language = "English",
volume = "40",
pages = "123--30",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "1",

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Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians. / Linneberg, A; Gonzalez-Quintela, A; Vidal, C; Jørgensen, T; Fenger, M; Hansen, Torben; Pedersen, O; Husemoen, L L N.

I: Clinical and Experimental Allergy, Bind 40, Nr. 1, 01.01.2010, s. 123-30.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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, T

AU - Fenger, M

AU - Hansen, Torben

AU - Pedersen, O

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

VL - 40

SP - 123

EP - 130

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 1

ER -