{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:13:08Z","timestamp":1779199988274,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Major depressive disorder is a highly prevalent psychological disorder worldwide and its main treatment is the use of Selective Serotonin Reuptake Inhibitors. However, few studies have demonstrated the relationship between the presence of genetic variants in pharmacogenes and the efficacy of these drugs, especially in populations with a unique genetic profile, such as the Indigenous peoples of the Amazon. Our study characterized the molecular profile of nine genes related to drug administration, metabolization, distribution, and elimination pathways and pharmacodynamic mechanisms of drug response through Whole Exome Sequencing applied in 64 Indigenous located in the Amazon. We compared the allele frequencies of the variants in Indigenous peoples and other world populations using Fisher's exact test carried out in RStudio v.3.5.1. We identified a total of 125 variants, of which 6 are possible new variants in our population on the\n                    <jats:italic>HTR2A<\/jats:italic>\n                    ,\n                    <jats:italic>HTR2C<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    , and\n                    <jats:italic>CYP1A2<\/jats:italic>\n                    genes. At least 9 variants showed a significant difference in the Indigenous population compared with other populations worldwide. Our study reaffirms the unique genetic profile of the Brazilian Amazon Indigenous population and allows us to contribute population\u2010specific variants that may serve as future pharmacogenomic biomarkers that help in the understanding of the individual genetic profiles of Indigenous people. Although the present study does not evaluate clinical drug response, the characterization of these variants provides a foundation for future studies exploring their potential impact on antidepressant efficacy in Indigenous populations and the application of this knowledge in the development of specific treatment protocols guided by pharmacogenomics.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70207","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:06:01Z","timestamp":1768565161000},"page":"1331-1339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomics of Major Depressive Disorder in Indigenous Amazonian Populations"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7751-2693","authenticated-orcid":false,"given":"Kaio Evandro Cardoso","family":"Aguiar","sequence":"first","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha Monte","family":"da Silva","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Carla Gomes","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Maur\u00edcio","family":"Ribeiro\u2010dos\u2010Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Human and Medical Genetics, Institute of Biological Science Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro Jos\u00e9","family":"de Souza","sequence":"additional","affiliation":[{"name":"Brain Institute Federal University of Rio Grande do Norte  Natal RN Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c2ndrea","family":"Ribeiro\u2010dos\u2010Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Human and Medical Genetics, Institute of Biological Science Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Farias","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"},{"name":"Laboratory of Human and Medical Genetics, Institute of Biological Science Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidney Emanuel Batista","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"},{"name":"Laboratory of Human and Medical Genetics, Institute of Biological Science Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne Rodrigues","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ney Pereira Carneiro","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Oncology Research Center Federal University of Par\u00e1  Bel\u00e9m, Par\u00e1 PA Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-019-05129-3"},{"key":"e_1_2_10_2_1","unstructured":"World Health Organization. <https:\/\/www.who.int\/publications\u2010detail\u2010redirect\/9789240049338> Accessed May 02 2024."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2019.01.003"},{"key":"e_1_2_10_4_1","first-page":"312","article-title":"Farmacogenetica in de psychiatrie; de huidige status quo [Pharmacogenetics in psychiatry; current status quo]","volume":"64","author":"Westrhenen R.","year":"2022","journal-title":"Tijdschr. Psychiatr."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2016.03.008"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12111758"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cppeds.2017.12.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.09.011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43610-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2573-6_21"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40142-013-0017-3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12060952"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67312-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy11040125"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1180487"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12312"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10709-016-9894-1"},{"key":"e_1_2_10_18_1","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J.","year":"1989"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14145102"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.19"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666201023154049"},{"key":"e_1_2_10_22_1","unstructured":"The pharmacogene variation (PharmVar) consortium\u2010 CYP1A2https:\/\/www.pharmvar.org\/gene\/CYP1A2."},{"key":"e_1_2_10_23_1","unstructured":"CPIC.CPIC\u00ae guideline for selective serotonin reuptake inhibitors and CYP2D6 and CYP2C19<https:\/\/cpicpgx.org\/guidelines\/cpic\u2010guideline\u2010for\u2010ssri\u2010and\u2010snri\u2010antidepressants\/>."},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2903"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14113861"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S281623"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18050665"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13030499"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13020368"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16030359"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.4.070802.110226"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-021-02415-y"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144884"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2011.47.6.1611895"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14071358"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1237446"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.08.004"},{"key":"e_1_2_10_38_1","volume-title":"Medical Genetics Summaries","author":"Dean L.","year":"2012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810916106"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10717-9"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0644-7"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041927"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70207","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70207","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:57:30Z","timestamp":1779199050000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/cpt.70207"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70207","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}