Genetic polymorphisms associated with upper gastrointestinal bleeding: A systematic review protocol

Abstract

Gastrointestinal bleedings (GIB) are one of the most frequent adverse drug reactions. Among the GIB upper gastrointestinal bleeding (UGIB) stands out due to their high mortality. The different idiosyncratic responses related to UGIB in medication users may be due to the presence of genetic variants in the genes that encode enzymes that are targets of pharmacokinetic and pharmacodynamic activity of the metabolism of the drugs, such as cyclooxygenase 1, endothelial nitric oxide synthase, cytochrome P450, among others. Although a review has focused on assessment whether the presence of CYP2C9*2 and CYP2C9*3 could increase UGIB diagnosis, the search is outdated, and more evidence can be identified regarding both CYP polymorphisms and other genes potentially involved with UGIB. The objective of the systematic review is to explore case-control or case-case studies to assess the epidemiological association between genetic polymorphisms and UGIB. This review will consider genetic polymorphisms of case-control and case-case studies and their association with the UGIB, in the presence or absence of drugs exposure. Electronic searches will be performed in PubMed, Scopus and the Cochrane Library with no time limit. Two researchers will select registries and extract data on study and population characteristics, exposure, covariates, and outcomes. Critical appraisal will consider Joanna Briggs tool for case-control studies. Studies will, where possible, be pooled with statistical meta-analysis. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate.