The Single Nucleotide Polymorphism Rs11643718 Inslc12a3is Associated With The Development Of Diabetic Kidney Disease In Chinese People With Type 2 Diabetes

Aims To examine the association between 24 literature-based single nucleotide polymorphisms and diabetic kidney disease in Chinese people with type 2 diabetes. Methods and results Twenty-four candidate diabetic kidney disease-susceptible single nucleotide polymorphisms were genotyped in 208 participants with type 2 diabetes and diabetic kidney disease and 200 participants with type 2 diabetes without diabetic kidney disease (case and control groups, respectively), together with 206 healthy participants using MassARRAY. Rs11643718 in theSLC12A3gene was associated with diabetic kidney disease in the recessive model after adjusting for confounding factors, such as age and gender (adjusted odds ratio 2.056, 95% CI 1.120-3.776;P= 0.020). Meta-analyses further confirmed the association (P= 0.002). In addition, participants with theGGgenotype had worse renal function and more albuminuria than those with theAA+AGgenotype (P< 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease andAA+AGorGGgenotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance ofSLC12A3was reduced in patients with theGGgenotype, while elevated expression ofSLC12A3was associated with better renal function. In addition, rs10951509 and rs1345365 inELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjustedP= 0.010 and 0.015, respectively). Conclusions TheGallele andGGgenotype ofSLC12A3rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes.