A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans

Michael V. Osier, Andrew J. Pakstis, David Goldman, Howard Edenberg, Judith R. Kidd, Kenneth K. Kidd

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: The alcohol dehydrogenase (ADH) genes have been repeatedly associated with protection against alcoholism. Until now, only four protein coding variants have been identified (ADH1C Arg271Gln, Ile349Val, ADH1B Arg47His, and Arg369Cys), and only two of these (ADH1C Ile349Val and ADH1B Arg47His) have been routinely tested in association studies with alcoholism. Methods: The newADH1C*351Thr allele was identified by direct sequencing of DNA samples that gave different typing results for the ADH1C Ile349Val polymorphism with different typing protocols. Results: A new coding variant has been identified at codon 351 of ADH1C. This allele is found in most Native American populations that we have studied with allele frequencies of the new ADH1C*351Thr allele as high as 26%. Only two instances of this allele have been seen in a large survey of African and Eurasian populations. Conclusions: The changes in charge, size, and rotational mobility caused by this amino acid substitution should be significant. Because this new variant codes for a new enzyme form in Native Americans, the kinetics of this enzyme should be studied and considered in studies of the role of ADH1C in the protection against alcoholism in Native Americans.

Original languageEnglish
Pages (from-to)1759-1763
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number12
StatePublished - Dec 1 2002

Fingerprint

North American Indians
Threonine
Proline
Codon
Substitution reactions
Alleles
Alcoholism
Alcohol Dehydrogenase
Enzymes
Polymorphism
Genes
Association reactions
Amino Acids
Kinetics
DNA
Amino Acid Substitution
DNA Sequence Analysis
Gene Frequency
Population
Proteins

Keywords

  • Alcohol Dehydrogenase
  • Allele Frequency
  • Coding Variation
  • Linkage Disequilibrium

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Osier, M. V., Pakstis, A. J., Goldman, D., Edenberg, H., Kidd, J. R., & Kidd, K. K. (2002). A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans. Alcoholism: Clinical and Experimental Research, 26(12), 1759-1763.

A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans. / Osier, Michael V.; Pakstis, Andrew J.; Goldman, David; Edenberg, Howard; Kidd, Judith R.; Kidd, Kenneth K.

In: Alcoholism: Clinical and Experimental Research, Vol. 26, No. 12, 01.12.2002, p. 1759-1763.

Research output: Contribution to journalArticle

Osier, MV, Pakstis, AJ, Goldman, D, Edenberg, H, Kidd, JR & Kidd, KK 2002, 'A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans', Alcoholism: Clinical and Experimental Research, vol. 26, no. 12, pp. 1759-1763.
Osier, Michael V. ; Pakstis, Andrew J. ; Goldman, David ; Edenberg, Howard ; Kidd, Judith R. ; Kidd, Kenneth K. / A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans. In: Alcoholism: Clinical and Experimental Research. 2002 ; Vol. 26, No. 12. pp. 1759-1763.
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