O impacto de polimorfismos de receptores e da via de ativação de glicocorticoides na evolução de pacientes com Arterite de

• Grant number: 21/12331-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2021
• End date: November 30, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre Wagner Silva de Souza
• Grantee: Andressa de Souza Moreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Takayasu arteritis (TAK) is a chronic granulomatous systemic vasculitis of unknown etiology, which causes structural alterations in large vessels, involving the aorta and its main branches, and pulmonary arteries. The main treatment of TAK is by using glucocorticoids (GC) in high doses, this medicament has polymorphic effects and can cause different adverse effects (AE). Some single nucleotide polymorphisms (SNP) are known to cause genetic variations in GC receptors or in its metabolism enzyme. Therefore, depending on the SNP, it is possible to have more or less of GC´s effect. Objective: This research project aims to evaluate the influence of certain SNPs of the HSD11B1 gene and the polymorphisms of the NR3C1 gene on the efficacy and toxicity of GC therapy in patients with TAK. Patients and methods: A retrospective cohort study will be conducted in patients with TAK who meet the classification criteria of the American College of Rheumatology for TAK. The medical records will be evaluated and there will be extraction of DNA samples and their genotyping to detect the SNPs of interest in these patients, using the Taqman allelic discrimination assay. The following SNPs will be investigated: rs11119328 of the HSD11B1 gene, and the SNPs rs6189, Bcl-1 (rs41423247), ER22 / 23EK (rs6189 and rs6190), and rs6198 of the NR3C1 gene. The results of genotyping the SNPs of the NR3C1 gene will be analyzed to distinguish five different haplotypes, using the PHASE program, which reconstructs the haplotypes by Bayesian analysis. Associations regarding response to therapy, patterns of GC use, and GC toxicity in TAK will be analyzed for the presence of the SNPs of the HSD11B1 and NR3C1 genes, as well as the SNP haplotypes of the NR3C1 gene.(AU)