Variants in the N-acetyltranferase 2 gene, acetylator phenotypes and their association with tuberculosis: Findings in Peruvian patients

Sánchez R.; Acosta O.; Laymito L.; Oscanoa T.; Guevara-Fujita M.; Moscol S.; Obispo D.; Huerta D.; Fujita R. · Journal of Clinical Tuberculosis and Other Mycobacterial Diseases (2024) · DOI: 10.1016/j.jctube.2024.100485

Resumen

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 N-acetyltransferase 2 (NAT2) gene are related to xenobiotic metabolism and have potential usefulness in TB studies. Aim: To determine whether NAT2 gene variants and acetylator phenotypes are associated with active TB in Peruvian patients. Methods: This study included cases (patients with TB) and controls (population-based data). First, DNA isolation and the rs1799929, rs1799930, and rs1799931 variants of the NAT2 gene were identified using sequencing methods. Subsequently, the acetylator phenotypes, namely slow (SA), intermediate (IA), and rapid acetylation (RA), were also analyzed. Results: The comparison of the frequencies of the rs1799931 variant in the cases and controls revealed significant differences. Risk factors were found for both the A allele (p = 0.00; odds ratio [OR] = 3.04, 95 % confidence interval [CI]: 1.88–4.9) and AG genotype (p = 0.00; OR = 5.94, 95 % CI: 3.17–11.09). In addition, the non-rapid acetylator phenotype (SA + IA) was also found to be a risk factor (p = 0.016; OR = 3.16, 95 % CI: 1.29–7.72). Conclusion: The A allele, GA heterozygous genotype of the rs1799931 variant of the NAT2 gene, and SA + IA acetylator phenotype showed an association with increased risk for the development of TB. In addition to xenobiotic metabolism, other metabolic and immunological functions of NAT2 have also been postulated to confer susceptibility to TB in the Peruvian population owing to its characteristic high Native American component.

Instituciones: Universidad Nacional Mayor de San Marcos; Universidad de San Martín de Porres