Identification of new genetic variants associated with the development of diabetic kidney disease by whole exome sequencing

Grant funding 2023-2025

"1. To identify novel genetic variants associated with a predisposition to the development of DKD, specifically in relation to ethnic/racial background.

2. To validate the identified variants, by investigating their prevalence in a large cohort of patients with Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM) with and without DKD.

3. To investigate the association of the detected variants with DKD-associated features, clinical and lifestyle risk factors, namely obesity, lipid metabolism, and psychological changes"

Diabetic kidney disease (DKD) is one of the main complications of Diabetes Mellitus (DM) and the leading cause of end-stage renal disease, requiring costly hemodialysis and kidney transplantation. In addition, DKD is typically associated with increased risk of cardiovascular disease and premature mortality. One in three of every DM patient will develop DKD, but, to date, the pathophysiological and molecular genetic mechanisms underlying the development of DKD remain poorly understood. A comprehensive understanding of molecular mechanisms involved in the development and progression of DKD, and genetic architecture of the latter may allow for the identification of new potential targets and facilitate the design of innovative therapeutic strategies.

Results obtained from this project will help in shaping future strategies to search for additional susceptibility genes in DKD, which in turn will have a significant impact in its diagnosis, management, and long-term follow up. In view of the heterogeneity of DKD, and its mode of presentation and prevalence among different races and communities, results obtained will be of direct significance to the population of Kazakhstan, where prevalence rates vary among its oblasts, and remains poorly managed and followed-up.