Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response
Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyure...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.553064/full |
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| author | Sètondji Cocou Modeste Alexandre Yahouédéhou Sètondji Cocou Modeste Alexandre Yahouédéhou Joelma Santana dos Santos Neres Caroline Conceição da Guarda Caroline Conceição da Guarda Suellen Pinheiro Carvalho Suellen Pinheiro Carvalho Rayra Pereira Santiago Rayra Pereira Santiago Camylla Vilas Boas Figueiredo Camylla Vilas Boas Figueiredo Luciana Magalhães Fiuza Luciana Magalhães Fiuza Uche Samuel Ndidi Rodrigo Mota de Oliveira Rodrigo Mota de Oliveira Cleverson Alves Fonseca Valma Maria Lopes Nascimento Larissa Carneiro Rocha Corynne Stéphanie Ahouéfa Adanho Tiago Santos Carvalho da Rocha Elisângela Vitória Adorno Marilda Souza Goncalves Marilda Souza Goncalves |
| author_facet | Sètondji Cocou Modeste Alexandre Yahouédéhou Sètondji Cocou Modeste Alexandre Yahouédéhou Joelma Santana dos Santos Neres Caroline Conceição da Guarda Caroline Conceição da Guarda Suellen Pinheiro Carvalho Suellen Pinheiro Carvalho Rayra Pereira Santiago Rayra Pereira Santiago Camylla Vilas Boas Figueiredo Camylla Vilas Boas Figueiredo Luciana Magalhães Fiuza Luciana Magalhães Fiuza Uche Samuel Ndidi Rodrigo Mota de Oliveira Rodrigo Mota de Oliveira Cleverson Alves Fonseca Valma Maria Lopes Nascimento Larissa Carneiro Rocha Corynne Stéphanie Ahouéfa Adanho Tiago Santos Carvalho da Rocha Elisângela Vitória Adorno Marilda Souza Goncalves Marilda Souza Goncalves |
| author_sort | Sètondji Cocou Modeste Alexandre Yahouédéhou |
| collection | DOAJ |
| description | Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers. |
| first_indexed | 2024-12-10T08:02:54Z |
| format | Article |
| id | doaj.art-3400dd841545442395b4388443304024 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T08:02:54Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3400dd841545442395b43884433040242022-12-22T01:56:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.553064553064Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea ResponseSètondji Cocou Modeste Alexandre Yahouédéhou0Sètondji Cocou Modeste Alexandre Yahouédéhou1Joelma Santana dos Santos Neres2Caroline Conceição da Guarda3Caroline Conceição da Guarda4Suellen Pinheiro Carvalho5Suellen Pinheiro Carvalho6Rayra Pereira Santiago7Rayra Pereira Santiago8Camylla Vilas Boas Figueiredo9Camylla Vilas Boas Figueiredo10Luciana Magalhães Fiuza11Luciana Magalhães Fiuza12Uche Samuel Ndidi13Rodrigo Mota de Oliveira14Rodrigo Mota de Oliveira15Cleverson Alves Fonseca16Valma Maria Lopes Nascimento17Larissa Carneiro Rocha18Corynne Stéphanie Ahouéfa Adanho19Tiago Santos Carvalho da Rocha20Elisângela Vitória Adorno21Marilda Souza Goncalves22Marilda Souza Goncalves23Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilDepartment of Biochemistry, Ahmadu Bello University, Zaria, NigeriaLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilAmbulatório, Fundação de Hematologia e Hemoterapia da Bahia, Salvador, BrazilAmbulatório, Fundação de Hematologia e Hemoterapia da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilLaboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Salvador, BrazilLaboratório de Pesquisa em Anemia, Departamento de Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BrazilDifferences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers.https://www.frontiersin.org/article/10.3389/fphar.2020.553064/fullsickle cell anemiahydroxyureaCYP2D6CYP3A4CATSLC14A1 |
| spellingShingle | Sètondji Cocou Modeste Alexandre Yahouédéhou Sètondji Cocou Modeste Alexandre Yahouédéhou Joelma Santana dos Santos Neres Caroline Conceição da Guarda Caroline Conceição da Guarda Suellen Pinheiro Carvalho Suellen Pinheiro Carvalho Rayra Pereira Santiago Rayra Pereira Santiago Camylla Vilas Boas Figueiredo Camylla Vilas Boas Figueiredo Luciana Magalhães Fiuza Luciana Magalhães Fiuza Uche Samuel Ndidi Rodrigo Mota de Oliveira Rodrigo Mota de Oliveira Cleverson Alves Fonseca Valma Maria Lopes Nascimento Larissa Carneiro Rocha Corynne Stéphanie Ahouéfa Adanho Tiago Santos Carvalho da Rocha Elisângela Vitória Adorno Marilda Souza Goncalves Marilda Souza Goncalves Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response Frontiers in Pharmacology sickle cell anemia hydroxyurea CYP2D6 CYP3A4 CAT SLC14A1 |
| title | Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response |
| title_full | Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response |
| title_fullStr | Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response |
| title_full_unstemmed | Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response |
| title_short | Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response |
| title_sort | sickle cell anemia variants in the cyp2d6 cat and slc14a1 genes are associated with improved hydroxyurea response |
| topic | sickle cell anemia hydroxyurea CYP2D6 CYP3A4 CAT SLC14A1 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.553064/full |
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