{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:19:05Z","timestamp":1774862345187,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Cat\u00f3lica de Santa Mar\u00eda\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/027ryxs60","award":["30248-R-2024"],"award-info":[{"award-number":["30248-R-2024"]}]},{"name":"PROCIENCIA","award":["PE501091237-2024-PROCIENCIA"],"award-info":[{"award-number":["PE501091237-2024-PROCIENCIA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Tuberculosis (TB) remains a major public health challenge in Peru, where interindividual variability in treatment response and drug-induced hepatotoxicity may be influenced by host genetic background. This study aimed to characterize clinically relevant polymorphisms in NAT2, CYP2E1, and SLCO1B1 in a cohort of TB patients from Southern Peru, a genetically underrepresented Andean population. Thirty-five adults receiving first-line therapy (isoniazid and rifampicin) underwent targeted Sanger sequencing of key functional variants among these three genes. NAT2 acetylator phenotypes were predominantly intermediate (68.6%), followed by rapid (20%) and slow (11.4%) profiles, with high minor allele frequencies for rs1041983 and rs1801280. CYP2E1 functional promoter variants were infrequent, whereas SLCO1B1 exhibited notable allelic heterogeneity, suggesting potential variability in rifampicin transport. Comparative analysis with previously reported Peruvian data revealed regional differences in acetylator distribution, supporting population-specific pharmacogenomic stratification. Although clinical toxicity outcomes were not evaluated, the high prevalence of reduced acetylation genotypes suggests a substantial proportion of patients may benefit from genotype-informed isoniazid dosing strategies. These findings provide foundational data for implementing precision medicine approaches using affordable and targeted technologies in TB management within Andean populations and support the integration of pharmacogenomics into national TB control programs.<\/jats:p>","DOI":"10.3390\/jpm16040184","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population-Specific Pharmacogenomic Profiling of NAT2, CYP2E1, and SLCO1B1 in Tuberculosis Patients from Southern Peru: A Feasibility Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0446-4430","authenticated-orcid":false,"given":"Tatiana","family":"Chavez-Arias","sequence":"first","affiliation":[{"name":"Escuela de Postgrado, Universidad Cat\u00f3lica de Santa Mar\u00eda, Arequipa 04013, Peru"},{"name":"\u00c1rea de Histocompatibilidad y Biolog\u00eda Molecular, Hospital Nacional Carlos Alberto Seguin Escobedo, Arequipa 04001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5229-0810","authenticated-orcid":false,"given":"Cecilia","family":"Manrique-Sam","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Humana, Universidad Cat\u00f3lica de Santa Mar\u00eda, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3795-898X","authenticated-orcid":false,"given":"Yuma","family":"Ita-Balta","sequence":"additional","affiliation":[{"name":"Escuela de Postgrado, Universidad Cat\u00f3lica de Santa Mar\u00eda, Arequipa 04013, Peru"},{"name":"Pathogen Genetics Research Group (PATHO-GEN), Organization for Medical Innovation and Collaboration for Science (OMICS), Lima 15001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Mont\u00e1nchez-Carazas","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Humana, Universidad Cat\u00f3lica de Santa Mar\u00eda, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-2608","authenticated-orcid":false,"given":"Alexis Germ\u00e1n","family":"Murillo Carrasco","sequence":"additional","affiliation":[{"name":"Pathogen Genetics Research Group (PATHO-GEN), Organization for Medical Innovation and Collaboration for Science (OMICS), Lima 15001, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Farf\u00e1n-Delgado","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Humana, Universidad Cat\u00f3lica de Santa Mar\u00eda, Arequipa 04013, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026). Tuberculosis, WHO. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/tuberculosis."},{"key":"ref_2","unstructured":"Ministerio de Salud (2024). Norma T\u00e9cnica de Salud para la Prevenci\u00f3n y Control de la Tuberculosis en el Per\u00fa, MINSA. Available online: https:\/\/cdn.www.gob.pe\/uploads\/document\/file\/8228140\/6873271-nts-para-la-prevencion-y-control-de-la-tb-2024.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/17425255.2018.1416093","article-title":"Pharmacokinetics and pharmacogenetics of anti-tubercular drugs: A tool for treatment optimization?","volume":"14","author":"Motta","year":"2018","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1440-1746.2007.05207.x","article-title":"Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review","volume":"23","author":"Tostmann","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tube.2007.05.012","article-title":"Genetic polymorphisms of NAT2 and CYP2E1 associated with antituberculosis drug-induced hepatotoxicity in Korean patients with pulmonary tuberculosis","volume":"87","author":"Cho","year":"2007","journal-title":"Tuberculosis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1111\/bcp.14758","article-title":"Relationship among genetic polymorphism of SLCO1B1, rifampicin exposure, and clinical outcomes in patients with active pulmonary tuberculosis","volume":"87","author":"Kim","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Meitei, H.N., Pandey, A., Faruquee, H.M., Thokchom, M., Athokpam, S., Guha, H., Das, R., and Haobam, R. (2021). Polymorphism of NAT2, PXR, ABCB1, and GSTT1 genes among tuberculosis patients of North Eastern States of India. medRxiv.","DOI":"10.1101\/2021.06.09.21258600"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"L\u00e9vano, K.S., Jaramillo-Valverde, L., Tarazona, D.D., S\u00e1nchez, C., Capristano, S., V\u00e1squez, T., Solari, L., Mendoza-Ticona, A., Soto, A., and Rojas, C. (2021). Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients. Mol. Genet. Genom. Med., 9.","DOI":"10.1002\/mgg3.1764"},{"key":"ref_9","unstructured":"Pe\u00f1aloza, P.A. (2020). Asociaci\u00f3n de Polimorfismos Gen\u00e9ticos en NAT2 con el da\u00f1o Hep\u00e1tico Inducido por Isoniacida en Pacientes con Tuberculosis Activa o Latent. [Master\u2019s Thesis, Universidad Nacional Mayor de San Marcos]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9006","DOI":"10.1021\/bi00425a019","article-title":"Human ethanol-inducible P450IIE1: Complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression","volume":"27","author":"Umeno","year":"1988","journal-title":"Biochemistry"},{"key":"ref_11","unstructured":"Valverde, L.J.J. (2023). Polimorfismos de los genes enzim\u00e1ticos NAT2, CYP2E1 y GST y presencia de reacci\u00f3n adversa a f\u00e1rmacos antituberculosos en la poblaci\u00f3n peruana. [Doctoral Thesis, Universidad Peruana Cayetano Heredia]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.5588\/ijtld.18.0324","article-title":"NAT2 genetic variants and toxicity related to anti-tubercular agents: A systematic review and meta-analysis","volume":"23","author":"Richardson","year":"2019","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, M.R., Huang, H.L., Lin, S.W., Cheng, M.H., Lin, Y.T., Chang, S.Y., Yan, B.-S., Kuo, C.-H., Lu, P.-L., and Wang, J.-Y. (2019). Isoniazid concentration and NAT2 genotype predict risk of systemic drug reactions during 3HP for LTBI. J. Clin. Med., 8.","DOI":"10.3390\/jcm8060812"},{"key":"ref_14","first-page":"474","article-title":"Association of cytochrome P450 2E1 and N-acetyltransferase 2 genotypes with serum isoniazid level and anti-tuberculosis drug-induced hepatotoxicity: A cross-sectional study","volume":"48","author":"Pourmohamadi","year":"2023","journal-title":"Iran. J. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11700","DOI":"10.1080\/21655979.2021.2003930","article-title":"Associations between liver damage and antituberculosis drug rifampicin and relative metabolic enzyme gene polymorphisms","volume":"12","author":"Su","year":"2021","journal-title":"Bioengineered"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000053376","article-title":"Sample size considerations in genetic polymorphism studies","volume":"52","year":"2001","journal-title":"Hum. Hered."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5808\/GI.2012.10.2.117","article-title":"Sample size and statistical power calculation in genetic association studies","volume":"10","author":"Hong","year":"2012","journal-title":"Genom. Inform."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"794","DOI":"10.17843\/rpmesp.2015.324.1774","article-title":"Rol de la farmacogen\u00f3mica en el r\u00e9gimen de tratamiento de tuberculosis","volume":"32","author":"Guio","year":"2015","journal-title":"Rev. Peru. Med. Exp. Salud Publica"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khan, S., Mandal, R.K., Elasbali, A.M., Dar, S.A., Jawed, A., Wahid, M., Mahto, H., Lohani, M., Mishra, B.N., and Akhter, N. (2019). Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid-induced hepatotoxicity: Trial sequential meta-analysis as evidence. Biosci Rep., 39.","DOI":"10.1042\/BSR20180845"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hoa, P.Q., Kim, H.K., Jang, T.W., Seo, H., Oh, J.Y., Kim, H.C., Shin, A.Y., Min, J., Jayanti, R.P., and Hung, T.M. (2024). Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure. Int. J. Antimicrob. Agents, 63.","DOI":"10.1016\/j.ijantimicag.2023.107034"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Soedarsono, S., Jayanti, R.P., Mertaniasih, N.M., Kusmiati, T., Permatasari, A., Indrawanto, D.W., Charisma, A.N., Lius, E.E., Yuliwulandari, R., and Hoa, P.Q. (2023). Development of population pharmacokinetics model and Bayesian estimation of rifampicin exposure in Indonesian patients with tuberculosis. Tuberculosis, 139.","DOI":"10.1016\/j.tube.2023.102325"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/4\/184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:36:41Z","timestamp":1774859801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/4\/184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":21,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jpm16040184"],"URL":"https:\/\/doi.org\/10.3390\/jpm16040184","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}