SLOW ACETYLATOR MUTATIONS IN THE HUMAN POLYMORPHIC N-ACETYLTRANSFERASE GENE IN 786 ASIANS, BLACKS, HISPANICS, AND WHITES - APPLICATION TO METABOLIC EPIDEMIOLOGY

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 amplifi cation 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 re sults show that four slow acetylator alleles can be detected as mutati ons at positions 481, 590, and 857 in the NAT2 gene. Recognized base s ubstitutions at positions 341 and 803 need not be determined, because they were almost always associated with the 481T mutation. The known m utation at position 282 was strongly associated with the 590A mutation . The 481T, 590A, and 857A mutations accounted for virtually all of th e slow acetylator alleles in Asian and white populations. The 857A mut ation proved to be an Asiatic allele. The results will be useful in la rge-scale epidemiologic studies of cancer and other conditions potenti ally associated with the acetylator polymorphism.