1993
DOI: 10.1006/abbi.1993.1116
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Structural Heterogeneity of Caucasian N-Acetyltransferase at the NAT1 Gene Locus

Abstract: The human N-acetylation polymorphism is a genetic trait phenotypically reflected by differences in N-acetyltransferase (NAT) activity with therapeutic agents (rapid and slow acetylation), but a genetic invariability in N-acetylation of some arylamine drugs is also known. There are two highly similar human NAT genes: NAT1 is thought to encode a genetically invariant protein, whereas NAT2 has conclusively been shown to represent a polymorphic locus. This study demonstrates the presence of discrete NAT1 structura… Show more

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Cited by 131 publications
(58 citation statements)
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“…However, wide inter-individual variability in NAT1 activity towards PABA or PAS 51,67-72 was suggestive of a genetic polymorphism, but NAT1 activities were generally unimodally distributed. It wasn't until 1993 when Vatsis and Weber 73 first reported the existence of several allelic variations at the NAT1 locus that interest in the NAT1 gene was aroused, marking the beginning of a systematic survey of NAT1 genotypes. To date, 26 different NAT1 alleles have been detected in human populations (Table 2; reviewed in 15,24,52 ), however, only a small number have been shown to alter phenotype in vivo.…”
Section: Human Nat1 Allelesmentioning
confidence: 99%
“…However, wide inter-individual variability in NAT1 activity towards PABA or PAS 51,67-72 was suggestive of a genetic polymorphism, but NAT1 activities were generally unimodally distributed. It wasn't until 1993 when Vatsis and Weber 73 first reported the existence of several allelic variations at the NAT1 locus that interest in the NAT1 gene was aroused, marking the beginning of a systematic survey of NAT1 genotypes. To date, 26 different NAT1 alleles have been detected in human populations (Table 2; reviewed in 15,24,52 ), however, only a small number have been shown to alter phenotype in vivo.…”
Section: Human Nat1 Allelesmentioning
confidence: 99%
“…However, recent functional studies suggest that there is an inter-individual inherited variation which is distinct from the allele type present at the AAC-2 locus (Cribb et al, 1991;Ward et al, 1992). Recently, different alleles at the AAC-J locus have been described (Vatsis and Weber, 1993). One of the alleles shows a point mutation in the coding region and there may be other alleles with deletions in the 3' non-coding region.…”
Section: Introductionmentioning
confidence: 99%
“…The NAT2 (139), which was until recently thought to be the only polymorphic N-acetyltransferase (NAT), is responsible for the well-known inherited interindividual variation in the ability to acetylate substrates such as the arylamine drugs procainamide and sulfamethazine, the arylamine carcinogen benzidine, and some hydrazine drugs such as isoniazid and hydralazine (137,138). Recently another human N-acetyltransferase, NATI (138), which is widely expressed in tissues (140) and cultured cells (141), has also been found to be polymorphic (142).…”
Section: Glutathione S-transferasesmentioning
confidence: 99%
“…The NA Tl *4allele is denoted as the wild type. A prominent change in one of the variants (NA TI *10), which has an alteration of the consensus polyadenylation signal (142), was recently reported to be associated with both higher NATI activity in bladder and colon tissue and DNA adduct levels in the colon tissues (152,153). Given that NATI has been reported to be primarily responsible for the NAT activity in the human uroepithelium (154) (161,169).…”
Section: Glutathione S-transferasesmentioning
confidence: 99%