Phenotypic and Genotypic Characterization of N-Acetylation

Svensson, Craig K.; Hein, David W.

doi:10.1385/1-59259-832-3:173

Cited by 2 publications

(1 citation statement)

References 78 publications

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“…For example, the G 191 A substitution common to the NAT2 * 14 gene cluster is relatively frequent in African populations (Delomenie et al, ; Loktionov et al, ), but it is virtually absent in Caucasian populations. NAT2 alleles possessing the C 190 T (R64W), G 191 A (R64Q), T 341 C (I114T), G 364 A (D122N), A 411 T (L137F), A 434 C (E145P), G 590 A (R197Q), and/or G 857 A (G286E) missense SNPs are associated with slow acetylator phenotypes (Leff et al, ; Fretland et al, ; Hein, ; Svensson and Hein, in press). The NAT2 slow acetylator phenotypes are most likely not homogenous, but rather reflect varying levels of slow acetylator phenotype due to different mechanisms among the various SNPs (Leff et al, ).…”

Section: Commentarymentioning

confidence: 99%

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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Section: Commentarymentioning

confidence: 99%

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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The expanding role of gene-based prescribing for phase II drug-metabolizing enzymes

Babalola,

Kotila,

Iwuchukwu

2023

AJPPS

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Clinical pharmacogenomics has expanded rapidly with the ability to translate evidence from basic science findings into actionable decisions guiding pharmacotherapy in – various disease states. Most findings with potential clinical relevance have been in drug-metabolizing enzymes where variation could cause interindividual differences in response and efficacy. Conventionally, these metabolizing enzymes are classified as Phase I and Phase II enzymes. Although Phase II enzymes are responsible for the metabolism of many drugs, research has focused more on variation in Phase I enzymes. Our aim in this review was to discuss from a historical to present context, the research on key variants in major Phase II enzymes and to summarize clinical pharmacogenetic association studies that could help guide future translation into practice. We evaluated pivotal articles in PubMed (1980–2022) on human pharmacogenomic studies (preclinical and clinical) of N-acetyltransferases (NATs), methyltransferases, glutathione transferases, sulfotransferases, and glucuronosyltransferases for the evidence of clinical applicability and utility. Of the 5 Phase II enzyme superfamilies reviewed, there is presently evidence to support clinical utility for gene-based prescribing for two of them. A third family (NATs) is evaluated as having strong likelihood for future utility in the pharmacological treatment of acquired immunodeficiency syndrome-associated opportunistic infections, tuberculosis, and endemic diseases.

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Phenotypic and Genotypic Characterization of N-Acetylation

Cited by 2 publications

References 78 publications

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

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

The expanding role of gene-based prescribing for phase II drug-metabolizing enzymes

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