{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:41:49Z","timestamp":1763037709576,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>PDE4B<\/jats:italic> (phosphodiesterase\u20104B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, <jats:italic>PDE4B<\/jats:italic> variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. <jats:italic>PDE4B<\/jats:italic> allele rs6683977.G, associated with genomic regions of Native American origin in US\u2010Hispanics (admixed among Native Americans, Europeans, and Africans), increases ALL relapse risk, contributing to an association between Native American ancestry and ALL relapse that disappeared with an extra\u2010phase of chemotherapy. This result insinuates that indigenous populations along the Americas may have high frequencies of rs6683977.G, but this has never been corroborated. We studied ancestry and <jats:italic>PDE4B<\/jats:italic> diversity in 951 healthy individuals from nine Latin American populations. In non\u2010admixed Native American populations rs6683977.G has frequencies greater than 90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in <jats:italic>PDE4B<\/jats:italic>\u2010intron\u20107, conforming haplotypes showing their highest worldwide frequencies in Native Americans (&gt;0.82). Our findings inform the discussion on the pertinence of an extra\u2010phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US\u2010Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent.<\/jats:p>","DOI":"10.1111\/cts.13266","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T08:54:07Z","timestamp":1646902447000},"page":"1400-1405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population genetics of <i>PDE4B<\/i> (phosphodiesterase\u20104B) in neglected Native Americans: Implications for cancer pharmacogenetics"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2775-1333","authenticated-orcid":false,"given":"Rennan Garcias","family":"Moreira","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"Centro de Laborat\u00f3rios Multiusu\u00e1rios Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia Maria","family":"Saraiva\u2010Duarte","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre Costa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology Heart Institute Medical School of University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-0851","authenticated-orcid":false,"given":"Martha","family":"Sosa\u2010Macias","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, CIIDIR Unidad Durango  Durango Mexico"},{"name":"RIBEF Ibero\u2010American Network of Pharmacogenetics and Pharmacogenomics  Badajoz Extremadura Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Galaviz\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, CIIDIR Unidad Durango  Durango Mexico"},{"name":"RIBEF Ibero\u2010American Network of Pharmacogenetics and Pharmacogenomics  Badajoz Extremadura Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4808-2896","authenticated-orcid":false,"given":"Meddly Lesley","family":"Santolalla","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"Universidad Peruana Cayetano Heredia  Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wagner C. 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