MOLECULAR EVALUATION OF VARIANTS IN RELATION TO THE RISK OF DEVELOPING STEROID-SENSITIVE NEPHROTIC SYNDROME IN A SAMPLE OF THE BRAZILIAN POPULATION

• Grant number: 24/08228-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mara Sanches Guaragna
• Grantee: José Ronaldo Alves Troleze
• 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. It can be secondary to infections, tumors, medications, or genetic variants. Primary NS consists of idiopathic cases, which are generally classified according to their response to corticosteroid treatment, with 10-20% not responding to treatment and being classified as steroid-resistant nephrotic syndrome (SRNS). The remaining 80-90% are classified as steroid-sensitive nephrotic syndrome (SSNS). However, in clinical practice, more complex scenarios exist, with patients experiencing frequent relapses (SSNS-FR) or becoming steroid-dependent (SSNS-SD). It is believed that among SSNS patients, there is immune system involvement, with T and B cells playing a role in SSNS pathogenesis. Besides these non-genetic causes, recent advances in genomics and molecular biology have been uncovering various single nucleotide variations (SNVs) as risk factors associated with SSNS in both HLA and non-HLA gene loci. The contribution of genetic factors to the prevalence and clinical course of SSNS cases has been more difficult to define, likely due to the more complex inheritance patterns and variable clinical expression characterized by relapse and remission. Considering the findings in ethnic and population groups from international samples, the aim of this study is to investigate the role of eight single nucleotide variants (SNVs), two in HLA genes: rs1071630 (HLA-DQA1) and rs1063355 (HLA-DQB1) and six in non-HLA genes: rs412175 (NPHS1), rs7759971 (AHI1), rs10817678 (TNFSF15), rs55730955 (CD28), rs28862935 (BTC), and rs2637678 (CALHM6), in relation to the risk of developing SSNS in a Brazilian cohort. The case sample will consist of approximately 200 children and adolescents under 18 years of age with SSNS, SSNS-FR, or SSNS-SD treated at the nephrology outpatient clinic of the Integrated Center for Nephrology at Unicamp, and the control sample will comprise 1,992 individuals from the Brazilian ABraOM population bank. Genotyping analyses will be performed using the TaqMan® Genotyping system, and association and statistical analyses will be conducted using R language. Discoveries regarding the association of genetic variants in various populations, especially in admixed populations such as the Brazilian population, are crucial for advancing the understanding of the genetic architecture of SSNS, in order to improve the comprehension of the association with specific clinical and molecular heterogeneity in each population.