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Molecular Research on Pharmacogenetics

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Guest Editor
Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, Fatebenefratelli-Sacco Hospital, University of Milano, 20122 Milano, Italy
Interests: precision medicine; genotyping; pharmacokinetic; pharmacodinamic; pharmacogenetic personalized medicine; genotype; genomics; pharmacogenomics; genes; DNA; RNA; epigenetic

Special Issue Information

Dear Colleagues,

Rapid advances in genomic technologies and molecular biology, such as DNA chips or microarray technology, allows for expanding pharmacogenetic testing from individual variants to entire genes, enabling the discovery of rare variants and new variant/gene drug associations. This has led to the transformation of pharmacogenetics into a key field of multidisciplinary research for the application of personalized medicine.

This Special Issue aims to discuss developments in pharmacogenetics methodology and how these developments have made it possible to assess the full extent of pharmacological variants and improve the identification, functional validation and mechanistic understanding of the interplay between genes and drugs.

Dr. Stefania Cheli
Guest Editor

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Keywords

  • pharmacogenetics
  • pharmacokinetics
  • pharmacodynamics
  • genotype
  • haplotype
  • biomarker
  • single-nucleotide polymorphism
  • genomic variant
  • genetic testing
  • adverse drug reactions
  • clinical implementation

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Published Papers (1 paper)

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Research

14 pages, 620 KiB  
Article
NAT2 Acetylation Status Predicts Hepatotoxicity During Antituberculosis Therapy: Cumulative Risk Analysis of a Multiethnic Cohort
by Marco Schiuma, Sofia Dinegro, Vera Battini, Alessandro Torre, Alice Covizzi, Aurora Civati, Miriam Galimberti, Ilaria Mariani, Giulia Mosini, Carla Carnovale, Agostino Riva, Andrea Gori, Spinello Antinori, Emilio Clementi, Sonia Radice and Stefania Cheli
Int. J. Mol. Sci. 2025, 26(8), 3881; https://doi.org/10.3390/ijms26083881 - 19 Apr 2025
Viewed by 108
Abstract
Antituberculosis drug-induced hepatotoxicity (ATDH) is a common adverse drug reaction often requiring treatment interruption, complicating tuberculosis management. The slow acetylator phenotype, characterized by reduced N-acetyltransferase 2 (NAT2) enzyme activity, is associated with increased hepatotoxicity risk, while rapid acetylators are associated with a higher [...] Read more.
Antituberculosis drug-induced hepatotoxicity (ATDH) is a common adverse drug reaction often requiring treatment interruption, complicating tuberculosis management. The slow acetylator phenotype, characterized by reduced N-acetyltransferase 2 (NAT2) enzyme activity, is associated with increased hepatotoxicity risk, while rapid acetylators are associated with a higher risk of therapeutic failure. This study investigates the association between the NAT2 acetylation phenotype and ATDH occurrence, with an emphasis on its predictive value in regard to a multiethnic population and its impact on the timing of ATDH onset. A retrospective observational study was conducted on tuberculosis patients treated at Luigi Sacco Hospital, Milan, Italy (July 2020–September 2023). The NAT2 genotyping identified slow and rapid/intermediate acetylators. Cumulative incidence analysis and Fine–Gray competing risks regression models were used to assess ATDH risk and onset timing. Among 102 patients, 21.6% developed ATDH, including 16.7% with slow and 4.9% with rapid/intermediate acetylators. ATDH onset was significantly earlier in regard to slow acetylators (median 0.5 vs. 2 months, interquartile range-IQR: 0.5–3 vs. 1.7–5.5). Slow acetylators were associated with a higher risk of developing ATDH (Sub-distribution hazard ratio, SHR = 3.05; 95% confidence interval-CI: 1.17–7.95; p = 0.02), even after adjusting for confounders. The NAT2 acetylation phenotype strongly influences ATDH risk and timing. Early acetylator status identification may enable dose adjustments, enhancing treatment safety. These findings highlight the role of pharmacogenetics in optimizing antituberculosis therapy by improving efficacy and minimizing toxicity. Full article
(This article belongs to the Special Issue Molecular Research on Pharmacogenetics)
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