The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/jpps.2023.11136 http://hdl.handle.net/11449/248556 |
Resumo: | Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user. |
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The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control studycytochrome P-450 CYP2C9non-steroidal anti-inflammatory agentspharmacogenomic variantsplatelet aggregation inhibitorsvitamin K epoxide reductasesPurpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)Department of Surgery School of Medicine University of São Paulo (USP)Department of Public Health Bauru School of Dentistry University of São Paulo (USP)Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São PauloDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Forgerini, Marcela [UNESP]Urbano, GustavoDe Nadai, Tales RubensBatah, Sabrina SetembreFabro, Alexandre TodorovicDe Carvalho Mastroianni, Patrícia [UNESP]2023-07-29T13:47:13Z2023-07-29T13:47:13Z2023-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11136http://dx.doi.org/10.3389/jpps.2023.11136Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, v. 26, p. 11136-.1482-1826http://hdl.handle.net/11449/24855610.3389/jpps.2023.111362-s2.0-85150751090Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiquesinfo:eu-repo/semantics/openAccess2024-06-24T13:44:55Zoai:repositorio.unesp.br:11449/248556Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-06-24T13:44:55Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
title |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
spellingShingle |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study Forgerini, Marcela [UNESP] cytochrome P-450 CYP2C9 non-steroidal anti-inflammatory agents pharmacogenomic variants platelet aggregation inhibitors vitamin K epoxide reductases |
title_short |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
title_full |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
title_fullStr |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
title_full_unstemmed |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
title_sort |
The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study |
author |
Forgerini, Marcela [UNESP] |
author_facet |
Forgerini, Marcela [UNESP] Urbano, Gustavo De Nadai, Tales Rubens Batah, Sabrina Setembre Fabro, Alexandre Todorovic De Carvalho Mastroianni, Patrícia [UNESP] |
author_role |
author |
author2 |
Urbano, Gustavo De Nadai, Tales Rubens Batah, Sabrina Setembre Fabro, Alexandre Todorovic De Carvalho Mastroianni, Patrícia [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Forgerini, Marcela [UNESP] Urbano, Gustavo De Nadai, Tales Rubens Batah, Sabrina Setembre Fabro, Alexandre Todorovic De Carvalho Mastroianni, Patrícia [UNESP] |
dc.subject.por.fl_str_mv |
cytochrome P-450 CYP2C9 non-steroidal anti-inflammatory agents pharmacogenomic variants platelet aggregation inhibitors vitamin K epoxide reductases |
topic |
cytochrome P-450 CYP2C9 non-steroidal anti-inflammatory agents pharmacogenomic variants platelet aggregation inhibitors vitamin K epoxide reductases |
description |
Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T13:47:13Z 2023-07-29T13:47:13Z 2023-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/jpps.2023.11136 Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, v. 26, p. 11136-. 1482-1826 http://hdl.handle.net/11449/248556 10.3389/jpps.2023.11136 2-s2.0-85150751090 |
url |
http://dx.doi.org/10.3389/jpps.2023.11136 http://hdl.handle.net/11449/248556 |
identifier_str_mv |
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, v. 26, p. 11136-. 1482-1826 10.3389/jpps.2023.11136 2-s2.0-85150751090 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11136 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803649328723525632 |