The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry
<b>Background/Objectives:</b> Genetic polymorphism of the dihydropyrimidine dehydrogenase gene (<i>DPYD</i>) is responsible for the variability found in the metabolism of fluoropyrimidines such as 5-fluorouracil (5-FU), capecitabine, or tegafur. The <i>DPYD</i> ge...
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2024-12-01
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| author | Mariela Guevara Carla González de la Cruz Fernanda Rodrigues-Soares Ernesto Rodríguez Caíque Manóchio Eva Peñas-Lledó Pedro Dorado Adrián LLerena |
| author_facet | Mariela Guevara Carla González de la Cruz Fernanda Rodrigues-Soares Ernesto Rodríguez Caíque Manóchio Eva Peñas-Lledó Pedro Dorado Adrián LLerena |
| author_sort | Mariela Guevara |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Genetic polymorphism of the dihydropyrimidine dehydrogenase gene (<i>DPYD</i>) is responsible for the variability found in the metabolism of fluoropyrimidines such as 5-fluorouracil (5-FU), capecitabine, or tegafur. The <i>DPYD</i> genotype is linked to variability in enzyme activity, 5-FU elimination, and toxicity. Approximately 10–40% of patients treated with fluoropyrimidines develop severe toxicity. The interethnic variability of <i>DPYD</i> gene variants in Afro-Latin Americans is poorly studied, thereby establishing a barrier to the implementation of personalized medicine in these populations. Therefore, the present study aims to analyze the frequency of <i>DPYD</i> variants with clinical relevance in the Dominican population and their association with genomic ancestry components. <b>Methods:</b> For this study, 196 healthy volunteers from the Dominican Republic were genotyped for <i>DPYD</i> variants by qPCR, and individual genomic ancestry analysis was performed in 178 individuals using 90 informative ancestry markers. Data from the 1000 Genomes project were also retrieved for comparison and increased statistical power. <b>Results and Conclusions</b>: The c.557A>G variant (decreased dihydropyrimidine dehydrogenase function) presented a frequency of 2.6% in the Dominican population. Moreover, the frequency of this variant is positively associated with African ancestry (r<sup>2</sup> = 0.67, <i>p</i> = 1 × 10<sup>−7</sup>), which implies that individuals with high levels of African ancestry are more likely to present this variant. HapB3 is completely absent in Dominican, Mexican, Peruvian, Bangladeshi, and all East Asian and African populations, which probably makes its analysis dispensable in these populations. The implementation of pharmacogenetics in oncology, specifically <i>DPYD</i>, in populations of Afro-Latin American ancestry should include c.557A>G, to be able to carry out the safe and effective treatment of patients treated with fluoropyrimidines. |
| format | Article |
| id | doaj-art-a6a0b5bb7fd34ad79f08f080c19f6049 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Pharmaceutics |
| spelling | doaj-art-a6a0b5bb7fd34ad79f08f080c19f60492025-01-24T13:45:33ZengMDPI AGPharmaceutics1999-49232024-12-01171810.3390/pharmaceutics17010008The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African AncestryMariela Guevara0Carla González de la Cruz1Fernanda Rodrigues-Soares2Ernesto Rodríguez3Caíque Manóchio4Eva Peñas-Lledó5Pedro Dorado6Adrián LLerena7Research and Development Department, Universidad Nacional Pedro Henríquez Ureña, Santo Domingo 10203, Dominican RepublicPersonalized Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, SpainPersonalized Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, SpainResearch and Development Department, Universidad Nacional Pedro Henríquez Ureña, Santo Domingo 10203, Dominican RepublicDepartment of Pathology, Genetic and Evolution, Biological and Natural Sciences Institute, Universidade Federal do Triângulo Mineiro, Uberaba 38025-350, BrazilPersonalized Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, SpainPersonalized Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, SpainPersonalized Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, Spain<b>Background/Objectives:</b> Genetic polymorphism of the dihydropyrimidine dehydrogenase gene (<i>DPYD</i>) is responsible for the variability found in the metabolism of fluoropyrimidines such as 5-fluorouracil (5-FU), capecitabine, or tegafur. The <i>DPYD</i> genotype is linked to variability in enzyme activity, 5-FU elimination, and toxicity. Approximately 10–40% of patients treated with fluoropyrimidines develop severe toxicity. The interethnic variability of <i>DPYD</i> gene variants in Afro-Latin Americans is poorly studied, thereby establishing a barrier to the implementation of personalized medicine in these populations. Therefore, the present study aims to analyze the frequency of <i>DPYD</i> variants with clinical relevance in the Dominican population and their association with genomic ancestry components. <b>Methods:</b> For this study, 196 healthy volunteers from the Dominican Republic were genotyped for <i>DPYD</i> variants by qPCR, and individual genomic ancestry analysis was performed in 178 individuals using 90 informative ancestry markers. Data from the 1000 Genomes project were also retrieved for comparison and increased statistical power. <b>Results and Conclusions</b>: The c.557A>G variant (decreased dihydropyrimidine dehydrogenase function) presented a frequency of 2.6% in the Dominican population. Moreover, the frequency of this variant is positively associated with African ancestry (r<sup>2</sup> = 0.67, <i>p</i> = 1 × 10<sup>−7</sup>), which implies that individuals with high levels of African ancestry are more likely to present this variant. HapB3 is completely absent in Dominican, Mexican, Peruvian, Bangladeshi, and all East Asian and African populations, which probably makes its analysis dispensable in these populations. The implementation of pharmacogenetics in oncology, specifically <i>DPYD</i>, in populations of Afro-Latin American ancestry should include c.557A>G, to be able to carry out the safe and effective treatment of patients treated with fluoropyrimidines.https://www.mdpi.com/1999-4923/17/1/8fluoropyrimidines<i>DPYD</i>cancerAfrican ancestrypharmacogenetics |
| spellingShingle | Mariela Guevara Carla González de la Cruz Fernanda Rodrigues-Soares Ernesto Rodríguez Caíque Manóchio Eva Peñas-Lledó Pedro Dorado Adrián LLerena The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry Pharmaceutics fluoropyrimidines <i>DPYD</i> cancer African ancestry pharmacogenetics |
| title | The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry |
| title_full | The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry |
| title_fullStr | The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry |
| title_full_unstemmed | The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry |
| title_short | The Frequency of <i>DPYD</i> c.557A>G in the Dominican Population and Its Association with African Ancestry |
| title_sort | frequency of i dpyd i c 557a g in the dominican population and its association with african ancestry |
| topic | fluoropyrimidines <i>DPYD</i> cancer African ancestry pharmacogenetics |
| url | https://www.mdpi.com/1999-4923/17/1/8 |
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