Genetic variants in the PTGS2 gene and the risk of upper gastrointestinal bleeding in low-dose aspirin users: a case-control study

• Grant number: 21/06865-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2021
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia de Carvalho Mastroianni
• Grantee: Ana Luísa Rodriguez Gini
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Genetic susceptibility to the occurrence of non-variceal upper gastrointestinal bleeding (UGIB) in low-dose aspirin (LDA) users has been suggested. In this sense, our research group is conducting an unprecedented pharmacogenetic study in the Brazilian population and until this moment the influence of ten genetic variants on the risk of UGIB (PTGS1, NOS3, VKOCR1, ABCB1 and CYP2C9 genes) were evaluated. Objective: Therefore, this scientific research proposal intends to investigate the influence of two genetic variants rs689466 and rs5275 located in the PTGS2 gene on the risk of UGIB in LDA users. Methodology: This is an experimental genetic study. DNA samples from 50 cases and 150 controls will be used. DNA samples are stored in a biorepository and were obtained through a case-control study. Cases: LDA users diagnosed with UGIB. Control: non LDA users. It was defined as dependent variable UGIB in LDA users and as an independent variable the presence of variants rs689466 and rs5275. Confounding variables are ethnicity, schooling, body mass index, family history of ulcer, personal history of gastrointestinal diseases, serology for Helicobacter pylori, comorbidities, drug therapy in use, and lifestyle habits. Genetic variants will be analyzed using real-time polymerase chain reaction with the TaqPath ProAmp assay (AppliedBiosystems, Foster City, USA). Data will be tabulated and entered into Research Electronic Data Capture (RedCap). The genotypic frequency will be analyzed using the Hardy-Weinberg Equilibrium and the data will be analyzed using logistic regression models (SPSS Program). This study was approved by the Research Ethics Committee (CAAE 53753115.4.0000.5440 and CAAE 53753115.4.3001.5426). Expected results: To investigate the genetic variants involved in the risk of UGIB in LDA users, in order to collaborate with evidence to promote patient safety and with public health policies. (AU)