Influence of variants in the TBXA2R gene and the risk of upper gastrointestinal bleeding in low-dose aspirin users: a Pharmacogenetic study

• Grant number: 23/06966-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: April 30, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia de Carvalho Mastroianni
• Grantee: Maria Paula Bessa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Introduction: Upper gastrointestinal bleeding secondary to complicated peptic disease (UGIB) can be a serious adverse drug reaction, especially in low-dose aspirin (LDA) users. Idiosyncratic responses to the use of this medicine, possibly due to the presence of genetic variants, have been discussed in clinical practice. Through a systematic review, three potential variants located in the gene TBXA2R are found to be promising in the scope of the UGIB and they are proposed in this project. Variants in this gene can compromise important physiological functions, since this gene plays a key role in the induction of platelet aggregation and hemostasis. Objective: To investigate the influence of genetic variants in the TBXA2R gene on the risk of UGIB in LDA users. Methodology: An experimental genetic study will be conducted with DNA samples from 50 cases and 189 controls obtained in a case-control study. Cases are defined as LDA users diagnosed with UGIB. Two control groups will be considered, with participants without gastrointestinal problems: 1) LDA users and 2) non-LDA users (healthy controls). UGIB in LDA users was defined as dependent variable and the presence of the variants rs2238631 (C > T), rs4807491 (G > A) e rs1131882 (G > A) as an independent variable. The genetic variants will be analyzed using the polymerase chain reaction in real time (7500 real time). The Hardy-Weinberg Equilibrium will be evaluated and the data will be analyzed through the design of logistic regression models. Expected results: Investigate whether the proposed variants are involved in the risk of UGIB in order to collaborate with evidence for the promotion of LDA user safety, in addition to translating the technical-scientific knowledge of the data obtained, writing a manuscript and an abstract for presentation at a scientific event.