Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients

J Diabetes Complications. 2016 Jul;30(5):798-802. doi: 10.1016/j.jdiacomp.2016.02.018. Epub 2016 Feb 27.

Abstract

Aim: We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients.

Methods: Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated.

Results: In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively).

Conclusions: Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes.

Keywords: ABCG2; Diabetic kidney disease; SLC2A9; Single nucleotide polymorphisms; Uric acid.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alleles
  • Case-Control Studies
  • China
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Glomerular Filtration Barrier
  • Glucose Transport Proteins, Facilitative / genetics*
  • Glucose Transport Proteins, Facilitative / metabolism
  • Humans
  • Kidney / physiopathology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Polymorphism, Single Nucleotide*
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism
  • Renal Insufficiency / blood
  • Renal Insufficiency / complications
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / physiopathology
  • Uremia / etiology
  • Uric Acid / blood

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human
  • Glucose Transport Proteins, Facilitative
  • NRXN2 protein, human
  • Nerve Tissue Proteins
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • RNA Splicing Factors
  • SF1 protein, human
  • SLC22A12 protein, human
  • SLC2A9 protein, human
  • Uric Acid