Mots-Clés

Genetics Kidney Transplantation GWAS FSGS

Description

Title: Genetic determinants of Focal Segmental Glomerulosclerosis (FSGS) recurrence in kidney transplanted patients

Supervisors: Sophie Limou (sophie.limou@univ-nantes.fr), Martin Morin (martin.morin@univ-nantes)

Location: Centre de Recherche Translationnelle en Transplantation et Immunologie (CR2TI), Inserm UMR1064, Institut de Transplantation en Urologie-Néphrologie (ITUN), CHU de Nantes, 30 bd Jean Monnet, Nantes.

Context: Focal Segmental Glomerulosclerosis (FSGS) is a chronic glomerular nephropathy characterized by generalized kidney podocytes injury progressively leading to end stage kidney disease (ESKD). FSGS represents 4% of all ESKD cases in the United States and nearly 80% of FSGS cases are from unknown etiology. There are currently no curative treatments for FSGS, and corticosteroids or other drugs are prescribed to slow down the progression toward the ESKD stage, which requires renal replacement therapy by dialysis or transplantation. Unfortunately, FSGS recurs in 30 to 50% of transplanted patients, likely caused by a circulating factor involved in the FSGS physiopathology that is yet to be identified. Understanding the molecular pattern of FSGS recurrence in kidney transplanted patients remains a challenge for the scientific community and no genetic approach has yet been performed. With this proposal, we aim to find key molecular factor(s) involved in FSGS resurgence in kidney transplanted patients by running the first genome-wide association study (GWAS).

Objectives: Blood samples from 163 kidney transplanted patients with a primary FSGS diagnosis were collected and genotyped, 69 of whom have experimented a relapse of FSGS after transplantation. The intern will perform a GWAS to identify frequent genetic variants and subsequently key factors associated with FSGS recurrence in transplanted patients. This internship will require the use of genomic and bioinformatics tools (e.g. Plink, Bcftools) and the manipulation of R packages.