Universidad Peruana Cayetano Heredia

Population genetics of PDE4B (Phosphodiesterase-4B) in neglected native americans: implications for cancer pharmacogenetics.

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dc.contributor.author Moreira, Rennan Garcias
dc.contributor.author Saraiva-Duarte, Julia Maria
dc.contributor.author Pereira, Alexandre Costa
dc.contributor.author Sosa-Macias, Martha
dc.contributor.author Galaviz-Hernandez, Carlos
dc.contributor.author Santolalla Robles, Meddly Leslye
dc.contributor.author Magalhaes, Wagner C. S.
dc.contributor.author Zolini, Camila
dc.contributor.author Leal, Thiago Peixoto
dc.contributor.author Balazs, Zsolt
dc.contributor.author Llerena, Adrian
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Mill, Jose Geraldo
dc.contributor.author Borda, Victor
dc.contributor.author Guio, Heinner
dc.contributor.author O'Connor, Timothy D.
dc.contributor.author Tarazona-Santos, Eduardo
dc.contributor.author Rodrigues-Soares, Fernanda
dc.date.accessioned 2022-03-23T16:54:21Z
dc.date.available 2022-03-23T16:54:21Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/11491
dc.description.abstract PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.G, associated with genomic regions of Native American origin in US-Hispanics (admixed between 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-phase 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 PDE4B diversity in 951 healthy individuals from 9 Latin American populations. In non-admixed Native American populations rs6683977.G has frequencies >90%, is in linkage disequilibrium with other ALL relapse associated and regulatory variants in PDE4B-intron-7, conforming haplotypes showing their highest worldwide frequencies in Native Americans (>0.82). Our findings inform the discussion on the pertinence of an extra-phase of chemotherapy in Native American populations, and exemplifies how knowledge generated in US-Hispanics is relevant for their even more neglected and vulnerable Native American ancestors along the American continent. en_US
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartofseries Clinical and Translational Science
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject genetics en_US
dc.subject PDE4B en_US
dc.subject Phosphodiesterase-4B en_US
dc.subject native americans en_US
dc.subject cancer pharmacogenetics en_US
dc.title Population genetics of PDE4B (Phosphodiesterase-4B) in neglected native americans: implications for cancer pharmacogenetics. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1111/cts.13266
dc.relation.issn 1752-8062


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