Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium
<b>Background/Objectives</b>: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines <i>CYP2D6</i>, <...
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2024-10-01
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| author | Mariela Guevara Fernanda Rodrigues-Soares Carla González de la Cruz Fernando de Andrés Ernesto Rodríguez Eva Peñas-Lledó Adrián LLerena CEIBA Consortium of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics RIBEF |
| author_facet | Mariela Guevara Fernanda Rodrigues-Soares Carla González de la Cruz Fernando de Andrés Ernesto Rodríguez Eva Peñas-Lledó Adrián LLerena CEIBA Consortium of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics RIBEF |
| author_sort | Mariela Guevara |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> alleles and genotypes in 197 healthy volunteers from the Dominican Republic, as part of the RIBEF-CEIBA collaborative network. <b>Methods</b>: The analysis focuses on the participants’ tri-hybrid genomic ancestry, with CYP alleles determined by real-time PCR and molecular ancestry inferred using 90 AIMs. Linear regression was used to associate ancestry components with CYP frequencies. <b>Results</b>: The average ancestry was 23.8% European, 42.6% Native American, and 33.6% African, the latter being higher than in most Latin American populations. Native American ancestry was also higher than expected. Predicted phenotype frequencies based on genotypes were 4.2% poor metabolizers (gPMs) and 3.6% ultrarapid metabolizers (gUMs) for CYP2D6, as well as 3% gPMs, 22.8% rapid metabolizers (gRMs), and 1.5% gUMs for CYP2C19. No gPM individuals were observed for CYP2C9. Certain alleles associated with decreased CYP2D6 activity (<i>*17</i> and <i>*29</i>) and increased CYP2C19 activity (<i>*17</i> and gUMs) were positively linked with African ancestry and negatively with Native American ancestry. Rare <i>CYP2C9</i> alleles (<i>*5</i> and <i>*6</i>) with clinical relevance were additionally found. <b>Conclusions</b>: These findings build on previous results from the RIBEF-CEIBA collaborative network, demonstrating differences in allele frequencies of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in relation to genomic ancestry. In summary, ethnicity must be considered in the development of pharmacogenetic guidelines for clinical application, research, and regulation to avoid widening the biotechnology gap and to allow Personalized Medicine to reach the entire world population. |
| format | Article |
| id | doaj-art-aa8f3da5e6c549d58df50f18597e8685 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-aa8f3da5e6c549d58df50f18597e86852024-11-26T18:17:49ZengMDPI AGPharmaceutics1999-49232024-10-011611139910.3390/pharmaceutics16111399Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA ConsortiumMariela Guevara0Fernanda Rodrigues-Soares1Carla González de la Cruz2Fernando de Andrés3Ernesto Rodríguez4Eva Peñas-Lledó5Adrián LLerena6CEIBA Consortium of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics RIBEFFacultad de Ciencias de la Salud, Universidad Nacional Pedro Henríquez Ureña, Santo Domingo 10514, Dominican RepublicFaculty of Medicine and Health Sciences, University Institute for Bio-Sanitary Research of Extremadura INUBE, University of Extremadura, 06006 Badajoz, SpainFaculty of Medicine and Health Sciences, University Institute for Bio-Sanitary Research of Extremadura INUBE, University of Extremadura, 06006 Badajoz, SpainDepartment of Analytical Chemistry and Food Technology, Faculty of Pharmacy, University of Castilla-La Mancha, 02008 Albacete, SpainFacultad de Ciencias de la Salud, Universidad Nacional Pedro Henríquez Ureña, Santo Domingo 10514, Dominican RepublicFaculty of Medicine and Health Sciences, University Institute for Bio-Sanitary Research of Extremadura INUBE, University of Extremadura, 06006 Badajoz, SpainFaculty of Medicine and Health Sciences, University Institute for Bio-Sanitary Research of Extremadura INUBE, University of Extremadura, 06006 Badajoz, Spain<b>Background/Objectives</b>: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> alleles and genotypes in 197 healthy volunteers from the Dominican Republic, as part of the RIBEF-CEIBA collaborative network. <b>Methods</b>: The analysis focuses on the participants’ tri-hybrid genomic ancestry, with CYP alleles determined by real-time PCR and molecular ancestry inferred using 90 AIMs. Linear regression was used to associate ancestry components with CYP frequencies. <b>Results</b>: The average ancestry was 23.8% European, 42.6% Native American, and 33.6% African, the latter being higher than in most Latin American populations. Native American ancestry was also higher than expected. Predicted phenotype frequencies based on genotypes were 4.2% poor metabolizers (gPMs) and 3.6% ultrarapid metabolizers (gUMs) for CYP2D6, as well as 3% gPMs, 22.8% rapid metabolizers (gRMs), and 1.5% gUMs for CYP2C19. No gPM individuals were observed for CYP2C9. Certain alleles associated with decreased CYP2D6 activity (<i>*17</i> and <i>*29</i>) and increased CYP2C19 activity (<i>*17</i> and gUMs) were positively linked with African ancestry and negatively with Native American ancestry. Rare <i>CYP2C9</i> alleles (<i>*5</i> and <i>*6</i>) with clinical relevance were additionally found. <b>Conclusions</b>: These findings build on previous results from the RIBEF-CEIBA collaborative network, demonstrating differences in allele frequencies of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in relation to genomic ancestry. In summary, ethnicity must be considered in the development of pharmacogenetic guidelines for clinical application, research, and regulation to avoid widening the biotechnology gap and to allow Personalized Medicine to reach the entire world population.https://www.mdpi.com/1999-4923/16/11/1399<i>CYP2D6</i><i>CYP2C9</i><i>CYP2C19</i>DominicanAfricanancestry |
| spellingShingle | Mariela Guevara Fernanda Rodrigues-Soares Carla González de la Cruz Fernando de Andrés Ernesto Rodríguez Eva Peñas-Lledó Adrián LLerena CEIBA Consortium of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics RIBEF Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium Pharmaceutics <i>CYP2D6</i> <i>CYP2C9</i> <i>CYP2C19</i> Dominican African ancestry |
| title | Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium |
| title_full | Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium |
| title_fullStr | Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium |
| title_full_unstemmed | Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium |
| title_short | Afro-Latin American Pharmacogenetics of <i>CYP2D6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> in Dominicans: A Study from the RIBEF-CEIBA Consortium |
| title_sort | afro latin american pharmacogenetics of i cyp2d6 i i cyp2c9 i and i cyp2c19 i in dominicans a study from the ribef ceiba consortium |
| topic | <i>CYP2D6</i> <i>CYP2C9</i> <i>CYP2C19</i> Dominican African ancestry |
| url | https://www.mdpi.com/1999-4923/16/11/1399 |
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