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

  1. A. Linneberg1,
  2. A. Gonzalez-Quintela2,
  3. C. Vidal3,
  4. T. Jørgensen1,
  5. M. Fenger4,
  6. T. Hansen5,6,
  7. O. Pedersen5,6,7,
  8. L. L. N. Husemoen1

Article first published online: 15 DEC 2009

DOI: 10.1111/j.1365-2222.2009.03398.x

Issue

Clinical & Experimental Allergy

Clinical & Experimental Allergy

Volume 40, Issue 1, pages 123–130, January 2010

Additional Information

How to Cite

Linneberg, A., Gonzalez-Quintela, A., Vidal, C., Jørgensen, T., Fenger, M., Hansen, T., Pedersen, O. and Husemoen, L. L. N. (2010), Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians. Clinical & Experimental Allergy, 40: 123–130. doi: 10.1111/j.1365-2222.2009.03398.x

Author Information

  1. 1

    Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark

  2. 2

    Department of Medicine, Complejo Hospitalario Universitario, Santiago de Compostela, Spain

  3. 3

    Department of Allergy, Complejo Hospitalario Universitario, Santiago de Compostela, Spain

  4. 4

    Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre, Denmark

  5. 5

    Steno Diabetes Center, Gentofte, Denmark

  6. 6

    Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

  7. 7

    Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

*Correspondence: A. Linneberg, Research Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark, 57 Nrd Ringvej, Building 84/85, DK-2600 Glostrup, Denmark. E-mail: alli@glo.regionh.dk

Publication History

  1. Issue published online: 15 DEC 2009
  2. Article first published online: 15 DEC 2009
  3. Submitted 23 April 2009; revised 4 September 2009; accepted 11 September 2009

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Keywords:

  • acetaldehyde dehydrogenase;
  • alcohol dehydrogenase;
  • alcohol drinking;
  • respiratory hypersensitivity

Summary

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.

Cite this as: A. Linneberg, A. Gonzalez-Quintela, C. Vidal, T. Jørgensen, M. Fenger, T. Hansen, O. Pedersen and L. L. N. Husemoen, Clinical & Experimental Allergy, 2010 (40) 123–130.

View Full Article (HTML) Get PDF (177K)