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Introduction: The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs.
Areas Covered: We describe and review data that more clearly defines the effects of haplotypes and genotypes on the expression of acetylator phenotype towards selected drugs within human hepatocytes in vitro, within human hepatocyte cultures in situ, and clinical measures such as bioavailability, plasma metabolic ratios of parent to N-acetyl metabolite, elimination rate constants and plasma half-life, and/or clearance determinations in human subjects. We review several drugs (isoniazid, hydralazine, sulfamethazine, amifampridine, procainamide, sulfasalazine, amonafide and metamizole) for which phenotype-guided therapy may be important. The value of pharmacogenomics-guided isoniazid therapy for the prevention and treatment of tuberculosis is presented as a paradigm for phenotype-dependent dosing strategies.
Expert Opinion: Studies in human subjects and cryopreserved human hepatocytes show evidence for rapid, intermediate and slow acetylator phenotypes, with further data suggesting genetic heterogeneity within the slow acetylator phenotype. Incorporation of more robust genotype/phenotypes relationships, including genetic heterogeneity within the slow acetylator phenotype, should lead to further advancements in both health outcomes and cost benefit for prevention and treatment of tuberculosis.
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http://dx.doi.org/10.1080/17425255.2021.1840551 | DOI Listing |
Monaldi Arch Chest Dis
December 2024
Department of Clinical Pharmacology, Topiwala National Medical College And Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai.
The N-acetyltransferase 2 (NAT2) gene exhibits substantial genetic diversity, leading to distinct acetylator phenotypes among individuals. In this study, we determine NAT2 gene polymorphisms in tuberculosis (TB) patients and analyze serum isoniazid (INH) concentrations across the various genotypes. An observational prospective cohort study involving 217 patients with pulmonary or extrapulmonary TB was carried out.
View Article and Find Full Text PDFJ Clin Tuberc Other Mycobact Dis
December 2024
Centro de Investigación de Genética y Biología Molecular, Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Peru.
Background: Tuberculosis (TB) is a highly prevalent chronic infectious disease in developing countries, with Peru being one of the most affected countries in the world. The variants of the -acetyltransferase 2 () gene are related to xenobiotic metabolism and have potential usefulness in TB studies.
Aim: To determine whether gene variants and acetylator phenotypes are associated with active TB in Peruvian patients.
J Immunoassay Immunochem
November 2024
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt.
Background: Although numerous mechanisms are involved in vitiligo pathogenesis, few studies correlate N-acetyltransferase 2 to this disease.
Aim: To assess the N-acetyltransferase 2 (rs1799929) gene and its serum levels in vitiligo patients.
Subjects And Methods: In this case-control study, 65 vitiligo cases were compared to 65 age- and sex-matched healthy controls.
Pharmacogenet Genomics
December 2024
Departamento de Pesquisa, Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Objectives: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon.
Methods: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred.
eNeurologicalSci
June 2024
Oregon Health & Science University, Portland, OR 97239, USA.
A case-control study of sporadic amyotrophic lateral sclerosis (ALS) in a mountainous village in the French Alps discovered an association of cases with a history of eating wild fungi (false morels) collected locally and initially identified and erroneously reported as . Specialist re-examination of dried specimens of the ALS-associated fungi demonstrated they were members of the group, namely , species that have been reported to contain substantially higher concentrations of gyromitrin than present in . Gyromitrin is metabolized to monomethylhydrazine, which is responsible not only for the acute oral toxic and neurotoxic properties of false morels but also has genotoxic potential with proposed mechanistic relevance to the etiology of neurodegenerative disease.
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