Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients

Kelly S. Levano, Luis Jaramillo-Valverde, David D. Tarazona, Cesar Sanchez, Silvia Capristano, Tania Vásquez-Loarte, Lely Solari, Alberto Mendoza-Ticona, Alonso Soto, Christian Rojas, Roberto Zegarra-Chapoñan, Heinner Guio

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4 Citas (Scopus)


Background: We determined the frequency of genetic polymorphisms in three anti-TB drug metabolic proteins previously reported: N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. Methods: We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. Results: Seventy-four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug-induced liver injuries. Sixty-four percent are homozygous for the wild-type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug-resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. Conclusions: This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.

Idioma originalInglés estadounidense
PublicaciónMolecular genetics & genomic medicine
EstadoIndizado - oct. 2021
Publicado de forma externa

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© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC


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