The single nucleotide polymorphism rs11643718 in SLC12A3 is 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 the SLC12A3 gene 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 the GG genotype had worse renal function and more albuminuria than those with the AA+AG genotype (P < 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease and AA+AG or GG genotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance of SLC12A3 was reduced in patients with the GG genotype, while elevated expression of SLC12A3 was associated with better renal function. In addition, rs10951509 and rs1345365 in ELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjusted P = 0.010 and 0.015, respectively). Conclusions The G allele and GG genotype of SLC12A3 rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes.
What's new? Many diabetic kidney disease (DKD)‐susceptible single‐nucleotide polymorphims (SNPs) in type 2 diabetes have been identified; however, the relationship between some SNPs and DKD is still controversial. The effect of several SNPs on DKD in Chinese populations with type 2 diabetes is also unclear.This study found that the G allele and GG genotype in SLC12A3 rs11643718, as well as the G allele and GG+AG genotype in ELMO1 rs10951509 and rs1345365, may be risk factors for DKD in Chinese type 2 diabetes populations.Analysing these genotypes in people with type 2 diabetes will be helpful in identifying populations with high risk of DKD.