Objective: Several algorithms have been proposed to reduce the genotyping effort and cost, while retaining the accuracy of N-acetyltransferase-2 (NAT2) phenotype prediction. Data from the 1000 Genomes (1KG) project and an admixed cohort of Black Brazilians were used to assess the accuracy of NAT2 phenotype prediction using algorithms based on paired single nucleotide polymorphisms (SNPs) (rs1041983 and rs1801280) or a tag SNP (rs1495741).
Methods: NAT2 haplotypes comprising SNPs rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931 were assigned according to the arylamine N-acetyltransferases database. Contingency tables were used to visualize the agreement between the NAT2 acetylator phenotypes on the basis of these haplotypes versus phenotypes inferred by the prediction algorithms.
Results: The paired and tag SNP algorithms provided more than 96% agreement with the 7-SNP derived phenotypes in Europeans, East Asians, South Asians and Admixed Americans, but discordance of phenotype prediction occurred in 30.2 and 24.8% 1KG Africans and in 14.4 and 18.6% Black Brazilians, respectively. Paired SNP panel misclassification occurs in carriers of NATs haplotypes *13A (282T alone), *12B (282T and 803G), *6B (590A alone) and *14A (191A alone), whereas haplotype *14, defined by the 191A allele, is the major culprit of misclassification by the tag allele.
Conclusion: Both the paired SNP and the tag SNP algorithms may be used, with economy of scale, to infer NAT2 acetylator phenotypes, including the ultra-slow phenotype, in European, East Asian, South Asian and American populations represented in the 1KG cohort. Both algorithms, however, perform poorly in populations of predominant African descent, including admixed African-Americans, African Caribbeans and Black Brazilians.
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http://dx.doi.org/10.1097/FPC.0000000000000225 | DOI Listing |
Pharmacogenet Genomics
January 2025
Department of Pharmacology & Toxicology and Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Objective: Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.
View Article and Find Full Text PDFClin Infect Dis
December 2024
III Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.
Background: Under standard therapies, the incidence of drug-induced liver injury (DILI) in patients with tuberculosis ranges from 2% to 28%. Numerous studies have identified the risk factors for antituberculosis DILI; however, none have been conducted in a multiethnic real-world setting. The primary outcome of the current study was to identify the risk factors that could be used as the best predictors of DILI in a multiethnic cohort.
View Article and Find Full Text PDFMonaldi 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.
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