Genetics of Diabetic Kidney Disease in Type 2 Diabetes: Candidate Gene Studies and Genome-Wide Association Studies (GWAS)

Abstract

Type 2 diabetes (T2D) is a multifactorial disorder which is predicted to rise from 537 to 643 million by 2030 according to International Diabetes Federation Atlas 2021. One of the major microvascular complications of T2D is diabetic kidney disease (DKD), earlier known as diabetic nephropathy which leads to end-stage renal disease (ESRD) and kidney failure. Kidney dialysis or transplantation is required for the ESRD patients which poses a socioeconomic burden worldwide. The prevalence of DKD in T2D is 25–40% worldwide and hence it is important to study the pathogenesis of DKD which will aid in understanding and treating the disease. It has been shown that hereditary factors (genes) play a crucial role in the pathogenesis and progression of DKD. A number of genes have been found to be associated with DKD using candidate gene approach and genome-wide association studies (GWAS). GWAS genotypes a large number of markers across cases and controls and finds out the genetic markers/polymorphisms which are significantly associated with the disease or a trait. This review focuses on the genetic understanding of DKD obtained from these GWA studies conducted between 2003 and 2022 and also covers the genes identified from the candidate gene approach.