title: A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans.
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 (ADH1CIle349Val and ADH1B Arg47His) have been routinely tested in association studies with alcoholism.
  
  
  METHODS
  The new ADH1C*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 in the protection against alcoholism in Native Americans.
authors.affiliation: Department of Genetics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Osier
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pakstis
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kidd
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Kidd
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D003062:Codon / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D011392:Proline / Q000235:genetics*; D013912:Threonine / Q000235:genetics*; D014481:United States
chemical_list: D003062:Codon; D013912:Threonine; D011392:Proline; D000426:Alcohol Dehydrogenase