A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy
Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically...
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| Published in | Journal of personalized medicine Vol. 11; no. 5; p. 400 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel
MDPI AG
12.05.2021
MDPI |
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| Online Access | Get full text |
| ISSN | 2075-4426 2075-4426 |
| DOI | 10.3390/jpm11050400 |
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| Abstract | Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals. |
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| AbstractList | Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals. Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals.Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals. |
| Author | Sambracos-Parrado, Santiago Panche, Karen Ruiz-Torres, Daniel-Armando Tamayo-Agudelo, Caroll Andrea Pardo-Oviedo, Juan Mauricio Contreras, Nora Castillo-León, Luisa-Fernanda Calderón-Ospina, Carlos Alberto Abaunza, Katherine Parra Angulo-Aguado, Mariana Niño-Orrego, Maria Jose Páez, Nathaly Piñeros-Hernandez, Laura B Laissue, Paul Fonseca-Mendoza, Dora Janeth |
| AuthorAffiliation | 3 Biopas Laboratoires, Orphan Diseases Unit, BIOPAS GROUP, 111111 Bogotá, Colombia 2 Internal Medicine Department, School of Medicine and Health Sciences, Hospital Universitario Mayor-Méderi, Universidad del Rosario, Carrera 24 N° 63C-69, 112111 Bogotá, Colombia; karen.panche@urosario.edu.co (K.P.); juan.pardo@urosario.edu.co (J.M.P.-O.); katherinea.parra@urosario.edu.co (K.P.A.) 1 Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Carrera 24 N° 63C-69, 112111 Bogotá, Colombia; mariana.anguloa@urosario.edu.co (M.A.-A.); caroll.tamayo@urosario.edu.co (C.A.T.-A.); danielar.ruiz@urosario.edu.co (D.-A.R.-T.); santiago.sambracosp@urosario.edu.co (S.S.-P.); mariaj.nino@urosario.edu.co (M.J.N.-O.); Nathalya.paez@urosario.edu.co (N.P.); laurab.pineros@urosario.edu.co (L.B.P.-H.); lu-casti@hotmail.com (L.-F.C.-L.); paullaissue@yahoo.com (P.L.); nora.contreras@urosario.edu.co (N.C.); carlos.calderon@urosari |
| AuthorAffiliation_xml | – name: 1 Center for Research in Genetics and Genomics—CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Carrera 24 N° 63C-69, 112111 Bogotá, Colombia; mariana.anguloa@urosario.edu.co (M.A.-A.); caroll.tamayo@urosario.edu.co (C.A.T.-A.); danielar.ruiz@urosario.edu.co (D.-A.R.-T.); santiago.sambracosp@urosario.edu.co (S.S.-P.); mariaj.nino@urosario.edu.co (M.J.N.-O.); Nathalya.paez@urosario.edu.co (N.P.); laurab.pineros@urosario.edu.co (L.B.P.-H.); lu-casti@hotmail.com (L.-F.C.-L.); paullaissue@yahoo.com (P.L.); nora.contreras@urosario.edu.co (N.C.); carlos.calderon@urosario.edu.co (C.A.C.-O.) – name: 2 Internal Medicine Department, School of Medicine and Health Sciences, Hospital Universitario Mayor-Méderi, Universidad del Rosario, Carrera 24 N° 63C-69, 112111 Bogotá, Colombia; karen.panche@urosario.edu.co (K.P.); juan.pardo@urosario.edu.co (J.M.P.-O.); katherinea.parra@urosario.edu.co (K.P.A.) – name: 3 Biopas Laboratoires, Orphan Diseases Unit, BIOPAS GROUP, 111111 Bogotá, Colombia |
| Author_xml | – sequence: 1 givenname: Mariana orcidid: 0000-0003-2724-2950 surname: Angulo-Aguado fullname: Angulo-Aguado, Mariana – sequence: 2 givenname: Karen surname: Panche fullname: Panche, Karen – sequence: 3 givenname: Caroll Andrea surname: Tamayo-Agudelo fullname: Tamayo-Agudelo, Caroll Andrea – sequence: 4 givenname: Daniel-Armando surname: Ruiz-Torres fullname: Ruiz-Torres, Daniel-Armando – sequence: 5 givenname: Santiago surname: Sambracos-Parrado fullname: Sambracos-Parrado, Santiago – sequence: 6 givenname: Maria Jose surname: Niño-Orrego fullname: Niño-Orrego, Maria Jose – sequence: 7 givenname: Nathaly surname: Páez fullname: Páez, Nathaly – sequence: 8 givenname: Laura B orcidid: 0000-0002-5274-9203 surname: Piñeros-Hernandez fullname: Piñeros-Hernandez, Laura B – sequence: 9 givenname: Luisa-Fernanda orcidid: 0000-0002-6529-413X surname: Castillo-León fullname: Castillo-León, Luisa-Fernanda – sequence: 10 givenname: Juan Mauricio orcidid: 0000-0003-0084-3449 surname: Pardo-Oviedo fullname: Pardo-Oviedo, Juan Mauricio – sequence: 11 givenname: Katherine Parra surname: Abaunza fullname: Abaunza, Katherine Parra – sequence: 12 givenname: Paul surname: Laissue fullname: Laissue, Paul – sequence: 13 givenname: Nora surname: Contreras fullname: Contreras, Nora – sequence: 14 givenname: Carlos Alberto orcidid: 0000-0002-7305-8727 surname: Calderón-Ospina fullname: Calderón-Ospina, Carlos Alberto – sequence: 15 givenname: Dora Janeth surname: Fonseca-Mendoza fullname: Fonseca-Mendoza, Dora Janeth |
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| SubjectTerms | Acute coronary syndromes Adenosine diphosphate Algorithms Alleles Blood platelets Clopidogrel Diabetes Drug dosages Enzymes Gene frequency Genetic analysis Genetic diversity Haplotypes Linkage disequilibrium Patients Population studies Precision medicine Regulatory sequences Software |
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| Title | A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy |
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