MOLECULAR EVALUATION OF VARIANTS RELATED TO GLUCOCORTICOID RESISTANCE IN PATIENTS WITH IDIOPATHIC NEPHROTIC SYNDROME

• Grant number: 25/09740-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mara Sanches Guaragna
• Grantee: Geovana Cardoso de Assis
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Nephrotic syndrome (NS), characterized by proteinuria, edema, hypoalbuminemia, and hyperlipidemia, is one of the most common kidney diseases in childhood. NS is classified according to the response to glucocorticoid treatment, with 10-20% classified as steroid-resistant (SRNS) and 80-90% as steroid-sensitive (SSNS). However, in clinical practice, more complex scenarios exist, with patients experiencing frequent relapses (FRNS) or being corticosteroid-dependent (SDNS). Genome-wide association studies have shown a relationship between single nucleotide variants (SNVs) and treatment response, including SNVs in the ABCB1 gene, which encodes P-glycoprotein (P-gp). Considering these findings from ethnic groups and international population samples, the aim of this study is to investigate the role of SNV rs1045642 in the ABCB1 gene regarding the risk of developing SRNS in a Brazilian population sample. The case sample will include approximately 150 individuals with SRNS followed at the glomerulopathy clinic of the Integrated Nephrology Center at Unicamp, and the control sample will consist of 1,780 individuals from the Brazilian population genome bank ABraOM. Genotyping analyses will be performed using the TaqMan® Genotyping system, and association and statistical analyses will be carried out using the R language. Findings regarding the association of this genetic variant in admixed populations, such as the Brazilian population, are essential for incorporating pharmacogenetics into the evaluation of patients with NS, with the goal of minimizing drug toxicity and enabling more personalized treatments. (AU)