Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1, and L1CAM in the Japanese population

Citation
A. Sekine et al., Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1, and L1CAM in the Japanese population, J HUM GENET, 46(6), 2001, pp. 314-319
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF HUMAN GENETICS
ISSN journal
1434-5161 → ACNP
Volume
46
Issue
6
Year of publication
2001
Pages
314 - 319
Database
ISI
SICI code
1434-5161(2001)46:6<314:IOSP(O>2.0.ZU;2-W
Abstract
By direct sequencing of regions of the human genome containing live genes b elonging to the acetyltransferase family, arylamine N-acetyltransferase (NA T1), arylamine N-acetyltransferase (NAT2), arylalkylamine N-acetyltransfera se (AANAT), L1 cell adhesion molecule (L1CAM). and the human homolog of Sac charomyces cerevisiae N-acetyltransferase ARDI, we identified 53 single-nuc leotide polymorphisms (SNPs) and two insertion/deletion polymorphisms in 48 healthy Japanese volunteers. NAT1 and NAT2 are so-called drug-metabolizing enzymes. In the NAT1 gene we found two SNPs and a 3-bp insertion/deletion polymorphism that corresponded to the NAT1*3, *10, and *18A/*18B alleles re ported in other populations. The frequencies of NAT1* alleles in our Japane se subjects were 52.6% for NAT1*4. 1.0% for NAT1*3, 40.6% for NAT1*10, 2.6% for NAT1*18A and 3.1% for NAT1*18B. In the NAT2 gene we found 32 SNPs and a 1-bp insertion/deletion polymorphism; 6 SNPs within the coding region wer e reported previously and belonged to the slow acetylator group (NAT2*5, NA T2*6 and NAT2*7), and 2 of the 8 SNPs in the 5 ' flanking region were repor ted in the dbSNP of GenBank, but the remaining 24 SNPs and the insertion/de letion polymorphism were novel. The frequencies of NAT2* alleles in Japanes e (51.3% for NAT2*4, 1.6% for *5B, 26.1% for *6A, 2.2% for *6B, 1.2% for *7 A, 10.1% for *7B, 7.4% for *12A, and 1.1% for *13) were significantly diffe rent from those reported in Caucasian populations. In the AANAT gene we fou nd 4 novel SNPs: 2 in the 5 ' Banking region, 1 in exon 4, and 1 in intron 3. In the two genes belonging to the N-terminal N-acetyltransferase family, we identified 9 SNPs, 7 of them novel, for ARDI, and six novel SNPs for L1 CAM. Variations at these loci may contribute to an understanding of the way in which different genotypes may affect the activities of human N-acetyltr ansferases. especially as regards the therapeutic efficacy of certain drugs and antibiotics.