VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorForgerini, Marcela-
Autor(es): dc.creatorUrbano, Gustavo-
Autor(es): dc.creatorde Nadai, Tales Rubens-
Autor(es): dc.creatorZanelli, Cleslei Fernando-
Autor(es): dc.creatorValentini, Sandro Roberto-
Autor(es): dc.creatorMastroianni, Patrícia de Carvalho-
Data de aceite: dc.date.accessioned2025-08-21T21:32:21Z-
Data de disponibilização: dc.date.available2025-08-21T21:32:21Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-06-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.15403/JGLD-4226-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241162-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241162-
Descrição: dc.descriptionBackground & Aims: Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR-rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB). Methods: A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis. Controls were participants admitted to surgical procedures not related to gastrointestinal problems. The 4b/4a VNTR was determined through polymerase chain reaction followed by fragment analysis. Conditional logistic regression models were designed. The additive interaction between the presence of the 4b/4a VNTR variant and the use of low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) was calculated by fitting the Cox regression model through the parameters of Synergism index (S) and Relative Excess Risk Due To Interaction (RERI). Results: The presence of the 4b/4a VNTR variant did not increase the risk of UGIB: carriers of the 4a/4a genotype (OR=0.37, 95%CI: 0.09-1.45) and of the variant allele “4a” (OR=0.91, 95%CI: 0.55-1.51). The risk of UGIB in LDA users carriers of the wild genotype (OR=4.96, 95%CI: 2.04-2.06) and the variant allele “4a” (OR=3.49, 95%CI: 1.18-10.38) is similar, as well as for NSAID users carriers of the wild genotype (OR=5.73, 95%CI: 2.61-12.60) and variant allele “4a” (OR=5.51, 95%CI: 1.42-15.82). No additive interaction was identified between the presence of the genetic variant and the use of LDA [RERI:-1.44 (95%CI:-6.02–3.14; S: 0.63 (95%CI:-1.97–1.15)] and NSAIDs [RERI:-0.13 (95%CI:-6.79–6.53; S: 0.97 (95%CI:-0.23–4.19)] on the UGIB risk. Conclusion: Our data suggests that there is no increase in the magnitude of UGIB risk in LDA and NSAIDs users’ carrying the variant allele “4a”.-
Descrição: dc.descriptionUniversidade Estadual Paulista-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Surgery School of Medicine University of São Paulo-
Descrição: dc.descriptionDepartment of Public Health Bauru School of Dentistry University of São Paulo (USP)-
Descrição: dc.descriptionDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)-
Descrição: dc.descriptionCAPES: 001-
Descrição: dc.descriptionFAPESP: 2017/24193-3-
Descrição: dc.descriptionFAPESP: 2018/07501-9-
Descrição: dc.descriptionCNPq: 401060/2014-4-
Formato: dc.format176-183-
Idioma: dc.languageen-
Relação: dc.relationJournal of Gastrointestinal and Liver Diseases-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectaspirin-
Palavras-chave: dc.subjectgastrointestinal bleeding-
Palavras-chave: dc.subjectnonsteroidal anti-inflammatory drugs-
Palavras-chave: dc.subjectNSAIDs-
Palavras-chave: dc.subjectpeptic ulcer hemorrhage-
Palavras-chave: dc.subjecttandem repeat sequences-
Palavras-chave: dc.subjectUGIB-
Palavras-chave: dc.subjectVNTR Sequences-
Título: dc.titleVNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study-
Tipo de arquivo: dc.typelivro digital-
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