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The single nucleotide polymorphism rs11643718 in SLC12A3 is associated with the development of diabetic kidney disease in Chinese people with type 2 diabetes
Author(s) -
Yang J.F.,
Xiong X.F.,
Xiao Y.,
Wei L.,
Li L.,
Yang M.,
Han Y.C.,
Zhao H.,
Li C.R.,
Jiang N.,
Xiong S.,
Zeng L.F.,
Zhou Z.G.,
Liu S.P.,
Wang N.S.,
Fan Y.,
Sun L.
Publication year - 2020
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.14364
Subject(s) - medicine , kidney disease , diabetes mellitus , single nucleotide polymorphism , type 2 diabetes , renal function , odds ratio , genotype , albuminuria , endocrinology , linkage disequilibrium , minor allele frequency , gastroenterology , genetics , biology , gene
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.