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Updated: Nov 7, 2025
Matrix-based DNA Extraction for Targeted Next-Generation Sequencing on Decontaminated Sputum Samples
Published on: June 6, 2025
NAT2 polymorphisms associated with the development of hepatotoxicity after first-line tuberculosis treatment in
Aldo Herrera-Rodulfo1, Mauricio Carrillo-Tripp2, Myrna Laura Yeverino-Gutierrez3
1Laboratorio de la Diversidad Biomolecular, Centro de investigación y de Estudios Avanzados del Instituto Politécnico Nacional Unidad Monterrey, Vía del Conocimiento 201, PIIT, C.P. 66600 Apodaca, Nuevo León, Mexico; Laboratorio de Ingeniería Genética y Genómica, Universidad Autónoma de Nuevo León, Vicente Guerrero s/n, Treviño, C.P. 64570 Monterrey, Nuevo León, Mexico; Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Calle 2 de abril - Jesús Dionisio González, Independencia, C.P. 64720 Monterrey, Nuevo León, Mexico.
Background And Aims:
To assess the relevance of the slow acetylator phenotype based on NAT2 genotypes, among patients with pulmonary tuberculosis (PTB) that developed hepatotoxicity after first-line tuberculosis treatment in a Northeastern Mexican population.
Methods:
Ninety one PTB patients were included, 7 of them developed hepatotoxicity. NAT2 SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931) were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using Epi Info statistical software 7.0 and SHEsisPlus for haplotype reconstruction. The NAT2 slow non-synonymous SNP were studied by molecular dynamic analysis (MDA).
Results:
The frequency of the haplotype associated with slow acetylation status for PTB was 58%, and for with hepatotoxicity (PTB-H) represented 42.6%. Three haplotypes, NAT2*5Q, NAT2*5U, NAT2*5Va were exclusively present in seven PTB-H patients, (P = 0.01, P = 0.0006, P = 0.01, respectively). These haplotypes include the combination of two SNPs (I114T + R197Q or I114T + G286E). The effect of the SNPs on protein structure is to disrupt the CoA binding site affecting acetylation activity.
Conclusion:
Our study provides insight into slow acetylation NAT2 haplotypes associated with hepatotoxicity after first-line tuberculosis treatment, for first time, in a Mexican population. The molecular mechanism acts at the CoA binding site.
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