IDENTIFICATION OF NEW GENETIC VARIANTS ASSOCIATED WITH THE DEVELOPMENT OF DIABETIC KIDNEY DISEASE

Abstract

Diabetic kidney disease (DKD) is a major complication of diabetes and a leading cause of chronic kidney disease. Despite its prevalence, the genetic and molecular mechanisms underlying DKD remain poorly understood, particularly in Central Asia, Kazakhstan. This study investigates the association between vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and microalbuminuria which is a key early marker of DKD, in a population with type 1 and type 2 diabetes in Kazakhstan. A cross-sectional study design was used, involving 257 participants stratified by the presence of microalbuminuria. Genetic analysis focused on four VDR SNPs: rs2228570, rs1544410, rs7975232, and rs731236. Statistical analyses adjusted for covariates such as age, sex, diabetes duration, and vitamin D levels. The results revealed that the rs2228570 VDR gene and biochemical characteristics related with metabolic dysregulation are associated with a higher risk of microalbuminuria in diabetic patients, whereas other tested SNPs are not associated with the kidney complication. There are no differences in the risk of microalbuminuria found with differences in treatments. Diabetic patients with low levels of vitamin D have a similar probability to avoid microalbuminuria and develop kidney complications. However, high vitamin D levels show protective properties against microalbuminuria. Therefore, vitamin D supplementation may contribute to the risk mitigation in case of no mutations in VDR genes but vitamin D supplements were not found to have any association with microalbuminuria. However, the study's limitations, including a relatively small sample size and reliance on self-reported data, underscore the need for further validation in larger, diverse populations. Future research should explore the functional mechanisms of identified SNPs and integrate additional covariates to refine risk prediction models and inform personalized treatment strategies for DKD.