Single nucleotide polymorphisms and the risk of upper gastrointestinal bleeding in users of acetylsalicylic acid as an antiplatelet agent: a case-control study

• Grant number: 24/06050-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: February 28, 2025
• 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: Genetic factors can influence the occurrence of upper gastrointestinal bleeding (UGIB) of non-variceal etiology, which is a serious adverse reaction. Previous studies have reported that variants in genes involved in processes that impact platelet aggregation increase the risk of gastrointestinal outcomes in users of acetylsalicylic acid (LDA). In this context, we selected nine genetic variants to investigate their influence on the risk of UGIB in LDA users. Objective: To investigate the influence of genetic variants in the AGT, IL-17F, UGT1A6, CYP2C19*17 and PTGS1 genes on the risk of UGIB in LDA users. Methodology: A case-control study will be conducted with DNA samples from 50 cases and 239 controls obtained in a case-control study. The cases were LDA users diagnosed with UGIB (n = 50). Two control groups were considered, with participants without gastrointestinal problems: 1) LDA users (n = 50) and 2) non-users of LDA (healthy controls) (n = 189). The genetic variants rs5050 (T > G), rs2397084 (T > C), rs763780 (T > C), rs2070959 (A > G), rs1105879 (A > C), rs12248560 (C > T), rs1330344 (C > T), rs3842787 (C > T) and rs3842788 (G > A) will be analyzed using real-time polymerase chain reaction (7500 real time). The Hardy-Weinberg Equilibrium will be assessed and the data will be analyzed using logistic regression models. Expected results: To investigate whether the proposed variants are involved in the risk of UGIB in LDA users, contributing to the advancement of pharmacogenetics in the individualization of therapy and in promoting the effectiveness and safety of patients with cardiovascular diseases. The translation of technical and scientific knowledge is also expected, as well as the preparation of a manuscript and abstract for presentation at a scientific event.