This work was funded in part by NIAAA grant AA09379. Support was also provided by grants from the Alfred P. Sloan Foundation (to KKK and JRK) and the NIH/NIGMS (GM57672 to KKK) for collection of population samples, and by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (to KKK).
A Proline-Threonine Substitution in Codon 351 of ADH1C Is Common in Native Americans
Version of Record online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 26, Issue 12, pages 1759–1763, December 2002
How to Cite
Osier, M. V., Pakstis, A. J., Goldman, D., Edenberg, H. J., Kidd, J. R. and Kidd, K. K. (2002), A Proline-Threonine Substitution in Codon 351 of ADH1C Is Common in Native Americans. Alcoholism: Clinical and Experimental Research, 26: 1759–1763. doi: 10.1111/j.1530-0277.2002.tb02481.x
- Issue online: 11 APR 2006
- Version of Record online: 11 APR 2006
- Received for publication September 5, 2002; accepted September 12, 2002.
- Alcohol Dehydrogenase;
- Coding Variation;
- Allele Frequency;
- Linkage Disequilibrium
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 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 ADH1C in the protection against alcoholism in Native Americans.