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. 1993 Apr;52(4):827–834.

Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology.

H J Lin 1, C Y Han 1, B K Lin 1, S Hardy 1
PMCID: PMC1682080  PMID: 8460648

Abstract

Our aim was to determine the population frequencies of the major slow acetylator alleles of the polymorphic N-acetyltransferase (NAT2) gene, whose locus maps to chromosome 8. We used allele-specific PCR amplification on 786 dried blood spots obtained from Hong Kong Chinese, U.S. Koreans, U.S. blacks, U.S. Hispanics, Germans, and U.S. whites. Our results show that four slow acetylator alleles can be detected as mutations at positions 481, 590, and 857 in the NAT2 gene. Recognized base substitutions at positions 341 and 803 need not be determined, because they were almost always associated with the 481T mutation. The known mutation at position 282 was strongly associated with the 590A mutation. The 481T, 590A, and 857A mutations accounted for virtually all of the slow acetylator alleles in Asian and white populations. The 857A mutation proved to be an Asiatic allele. The results will be useful in large-scale epidemiologic studies of cancer and other conditions potentially associated with the acetylator polymorphism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blum M., Demierre A., Grant D. M., Heim M., Meyer U. A. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5237–5241. doi: 10.1073/pnas.88.12.5237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DUFOUR A. P., KNIGHT R. A., HARRIS H. W. GENETICS OF ISONIAZID METABOLISM IN CAUCASIAN, NEGRO, AND JAPANESE POPULATIONS. Science. 1964 Jul 24;145(3630):391–391. [PubMed] [Google Scholar]
  3. Ellard G. A. Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin Pharmacol Ther. 1976 May;19(5 Pt 2):610–625. doi: 10.1002/cpt1976195part2610. [DOI] [PubMed] [Google Scholar]
  4. Grant D. M., Tang B. K., Kalow W. A simple test for acetylator phenotype using caffeine. Br J Clin Pharmacol. 1984 Apr;17(4):459–464. doi: 10.1111/j.1365-2125.1984.tb02372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Han C. Y., Lin B. K., Lin H. J. Methanol for preparing hair bulbs for PCR. Nucleic Acids Res. 1992 Dec 11;20(23):6419–6420. doi: 10.1093/nar/20.23.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harris C. C. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res. 1991 Sep 15;51(18 Suppl):5023s–5044s. [PubMed] [Google Scholar]
  7. Hein D. W. Acetylator genotype and arylamine-induced carcinogenesis. Biochim Biophys Acta. 1988 Aug 3;948(1):37–66. doi: 10.1016/0304-419x(88)90004-2. [DOI] [PubMed] [Google Scholar]
  8. Jinks D. C., Minter M., Tarver D. A., Vanderford M., Hejtmancik J. F., McCabe E. R. Molecular genetic diagnosis of sickle cell disease using dried blood specimens on blotters used for newborn screening. Hum Genet. 1989 Mar;81(4):363–366. doi: 10.1007/BF00283692. [DOI] [PubMed] [Google Scholar]
  9. Karim A. K., Elfellah M. S., Evans D. A. Human acetylator polymorphism: estimate of allele frequency in Libya and details of global distribution. J Med Genet. 1981 Oct;18(5):325–330. doi: 10.1136/jmg.18.5.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Khoury M. J., Adams M. J., Jr, Flanders W. D. An epidemiologic approach to ecogenetics. Am J Hum Genet. 1988 Jan;42(1):89–95. [PMC free article] [PubMed] [Google Scholar]
  11. Nebert D. W. Role of genetics and drug metabolism in human cancer risk. Mutat Res. 1991 Apr;247(2):267–281. doi: 10.1016/0027-5107(91)90022-g. [DOI] [PubMed] [Google Scholar]
  12. Ohsako S., Deguchi T. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. J Biol Chem. 1990 Mar 15;265(8):4630–4634. [PubMed] [Google Scholar]
  13. Perera F. P., Hemminki K., Gryzbowska E., Motykiewicz G., Michalska J., Santella R. M., Young T. L., Dickey C., Brandt-Rauf P., De Vivo I. Molecular and genetic damage in humans from environmental pollution in Poland. Nature. 1992 Nov 19;360(6401):256–258. doi: 10.1038/360256a0. [DOI] [PubMed] [Google Scholar]
  14. Probst M. R., Blum M., Fasshauer I., D'Orazio D., Meyer U. A., Wild D. The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Carcinogenesis. 1992 Oct;13(10):1713–1717. doi: 10.1093/carcin/13.10.1713. [DOI] [PubMed] [Google Scholar]
  15. Schurr T. G., Ballinger S. W., Gan Y. Y., Hodge J. A., Merriwether D. A., Lawrence D. N., Knowler W. C., Weiss K. M., Wallace D. C. Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages. Am J Hum Genet. 1990 Mar;46(3):613–623. [PMC free article] [PubMed] [Google Scholar]
  16. Shibata D. K., Arnheim N., Martin W. J. Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction. J Exp Med. 1988 Jan 1;167(1):225–230. doi: 10.1084/jem.167.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vatsis K. P., Martell K. J., Weber W. W. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6333–6337. doi: 10.1073/pnas.88.14.6333. [DOI] [PMC free article] [PubMed] [Google Scholar]

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