Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population

Connie J. Mulligan, Robert W. Robin, Michael V. Osier, Nyamkhishig Sambuughin, Lev G. Goldfarb, Rick A Kittles, Diane Hesselbrock, David Goldman, Jeffrey C. Long

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Enzymes encoded by two gene families, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDff), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADHlB*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current study, variants at ADH75(previously ADH2), ADH1C (previously ADH3), and ALDH2 were assayed in DNA extracts from participants belonging to a Southwest American Indian tribe (n=490) with a high prevalence of alcoholism. Each subject underwent a clinical interview for diagnosis of alcohol dependence, as well as evaluation of intermediate phenotypes such as binge drinking and flushing response to alcohol consumption. Detailed haplotypes were constructed and tested against alcohol dependence and related intermediate phenotypes using both association and linkage analysis. ADH and ALDH variants were also assayed in three Asian and one African population (no clinical data) in order to provide an evolutionary context for the haplotype data. Both linkage and association analysis identified several ADH 1C alleles and a neighboring microsatellite marker that affected risk of alcohol dependence and were also related to binge drinking. These data strengthen the support for ADH as a candidate locus for alcohol dependence and suggest further productive study.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalHuman Genetics
Volume113
Issue number4
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

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North American Indians
Alcoholism
Alcohols
Alcohol Dehydrogenase
Population
Genes
Binge Drinking
Alcohol Drinking
Haplotypes
Phenotype
Aldehyde Dehydrogenase
Acetaldehyde
Population Groups
Microsatellite Repeats
Alleles
Interviews
DNA
Enzymes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. / Mulligan, Connie J.; Robin, Robert W.; Osier, Michael V.; Sambuughin, Nyamkhishig; Goldfarb, Lev G.; Kittles, Rick A; Hesselbrock, Diane; Goldman, David; Long, Jeffrey C.

In: Human Genetics, Vol. 113, No. 4, 01.09.2003, p. 325-336.

Research output: Contribution to journalArticle

Mulligan, CJ, Robin, RW, Osier, MV, Sambuughin, N, Goldfarb, LG, Kittles, RA, Hesselbrock, D, Goldman, D & Long, JC 2003, 'Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population', Human Genetics, vol. 113, no. 4, pp. 325-336. https://doi.org/10.1007/s00439-003-0971-z
Mulligan, Connie J. ; Robin, Robert W. ; Osier, Michael V. ; Sambuughin, Nyamkhishig ; Goldfarb, Lev G. ; Kittles, Rick A ; Hesselbrock, Diane ; Goldman, David ; Long, Jeffrey C. / Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. In: Human Genetics. 2003 ; Vol. 113, No. 4. pp. 325-336.
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