Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas

Lin, Henry J.; Probst‐Hensch, Nicole; Hughes, Nicola; Sakamoto, Gordon T.; Louie, Andrew D.; Kau, Irving H; Lin, Bruce K.; Lee, David B.; Lin, Jesse; Frankl, Harold D.; Lee, Eric R.; Hardy, Steven; Grant, Denis M.; Haile, Robert W.

doi:10.1097/00008571-199806000-00009

Cited by 72 publications

(49 citation statements)

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“…16,79,81 Two other low activity alleles, NAT1*17 and NAT1*22, have been expressed in bacterial systems and both produced variant proteins that had no detectable NAT1 activity towards PAS. 18 Also, in the same study, immunoreactive NAT1 17 and NAT1 22 protein levels were markedly decreased compared with wild-type NAT1 4 protein levels. NAT1*19 was classified as a nonfunctional allele because the base substitution (C 97 T) introduces a premature stop codon.…”

Section: Human Nat1 Allelesmentioning

confidence: 63%

“…The most common low activity allele, NAT1*14, has been identified in Caucasian populations ranging from 1.3 to 3.7%. [16][17][18]79,81,82 Interestingly, a much higher frequency of the NAT1*14 allele (25%) was reported for a Lebanese population. 83 Since no homozygous individuals were identified in the above study, 50% of the Lebanese population had a slow acetylator genotype.…”

Section: Human Nat1 Allelesmentioning

confidence: 92%

“…The T 1088 A base change alters the consensus polyadenylation signal (AATAAA → AAAAAA) leading to the suggestion that increased activity may be due to enhanced mRNA stability. 74,78 However, several recent studies, [16][17][18]79,80 do not support the idea that the NAT1*10 allele is associated with elevated NAT1 activity. As a result, the functional significance of this allele remains unclear at present.…”

Section: Human Nat1 Allelesmentioning

confidence: 99%

“…NAT1*19 was classified as a nonfunctional allele because the base substitution (C 97 T) introduces a premature stop codon. 18 The effects of coding and 3′-noncoding polymorphisms in the NAT1*11 allele were characterised by de Leon and coworkers 80 recently. Using recombinant expression of NAT1*11 in both bacterial and mammalian systems, they showed that no major differences existed in catalytic or other properties of the NAT1 11 protein compared with wild-type NAT1 4 protein.…”

Section: Human Nat1 Allelesmentioning

confidence: 99%

“…This work provided a genetic understanding for the long known functional polymorphism in NAT2 activity 15 and, more recently, in NAT1 activity. [16][17][18] Genetic variation modulates the acetylator status of individuals and therefore may impact upon their predisposition to toxicity and disease. This review focuses on the genomics of the arylamine N-acetyltransferases and the impact of genetic variation of the enzymes on drug response in humans.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics of the arylamine N-acetyltransferases

et al. 2002

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The arylamine N-acetyltransferases (NATs) are involved in the metabolism of a variety of different compounds that we are exposed to on a daily basis. Many drugs and chemicals found in the environment, such as those in cigarette smoke, car exhaust fumes and in foodstuffs, can be either detoxified by NATs and eliminated from the body or bioactivated to metabolites that have the potential to cause toxicity and/or cancer. NATs have been implicated in some adverse drug reactions and as risk factors for several different types of cancers. As a result, the levels of NATs in the body have important consequences with regard to an individual's susceptibility to certain druginduced toxicities and cancers. This review focuses on recent advances in the molecular genetics of the human NATs.

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Section: Human Nat1 Allelesmentioning

confidence: 63%

Section: Human Nat1 Allelesmentioning

confidence: 92%

Section: Human Nat1 Allelesmentioning

confidence: 99%

Section: Human Nat1 Allelesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics of the arylamine N-acetyltransferases

et al. 2002

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TaqMan Real Time–Polymerase Chain Reaction Methods for Determination of Nucleotide Polymorphisms in Human N‐Acetyltransferase‐1 (NAT1) and ‐2 (NAT2)

Hein

Doll

2004

CP Toxicology

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N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) exhibit allelic variation and genetic polymorphism associated with increased susceptibility towards drug toxicity and environmental disease. TaqMan allelic discrimination methods are described to rapidly determine NAT1 and NAT2 genotypes. The SNPs selected for NAT1 genotype determinations are: C(97)T (R(33)Stop), C(190)T (R(64)W), G(445)A (V(149)I), C(559)T (R(187)Stop), G(560)A (R(187)Q), A(752)T (D(251)V), T(1088)A (3'UTR), and C(1095)A (3'UTR). The SNPs selected for NAT2 genotyping determinations are: G(191)A (R(64)Q), C(282)T (silent), T(341)C (I(114)T), C(481)T (silent), G(590)A (R(197)Q), A(803)G (K(268)R), and G(857)A (G(286)T). All NAT2 and NAT1 alleles, except very rare ones, are detected with these assays. Major advantages of the methods described in this unit are that they do not require post-PCR processing (such as enzyme digestion) or the use of radioactivity. Since the methods amplify relatively small segments of NAT1 or NAT2, they are effective for human DNA samples derived from buccal cells or paraffin-embedded tissues.

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