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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., 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.

Peru is a pluricultural and ethnically diverse country located in middle west of South America. It is the fourth largest country (1,285,216 km2) in area in South America, bordered in the north by Ecuador and Colombia, in the south by Chile, south east by Bolivia, by Brazil in the east and by the Pacific Ocean in the west. Peru has one of the most diverse climates, geographical and ecological in the world, from tropical or subtropical dessert to glacial in highland mountains to Amazon jungle. Peru is divided into 24 geopolitical regions with a central government. According to last national census in 2017, Peruvian populations accounts for 31,237,385 inhabitants (Instituto Nacional de Estadistica e Informatica [INEI], 2017). Most of Peru's population lives in the Coastal area, with almost one third of the nation's population living in Lima, the largest city with approximately 11 million people. Rural and urban population has changed over the last 50 years due to migration waves in the 1950s from rural to urban sites mainly located in the coast causing decrease or disappearance of native communities. Revisado por pares