Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease

Oxid Med Cell Longev. 2021 Sep 2:2021:2531062. doi: 10.1155/2021/2531062. eCollection 2021.


Diabetic type 2 patients compared to nondiabetic patients exhibit an increased risk of developing diabetic kidney disease (DKD), the leading cause of end-stage renal disease. Hyperglycemia, hypertension, oxidative stress (OS), and genetic background are some of the mechanisms and pathways implicated in DKD pathogenesis. However, data on OS pathway susceptibility genes show limited success and conflicting or inconclusive results. Our study is aimed at exploring OS pathway genes and variants which could be associated with DKD. We recruited 121 diabetes mellitus type 2 (DM2) patients with DKD (cases) and 220 DM2, non-DKD patients (control) of Greek origin and performed a case-control association study using genome-wide association data. PLINK and EIGENSOFT were used to analyze the data. Our results indicate 43 single nucleotide polymorphisms with their 21 corresponding genes on the OS pathway possibly contributing or protecting from DKD: SPP1, TPO, TTN, SGO2, NOS3, PDLIM1, CLU, CCS, GPX4, TXNRD2, EPHX2, MTL5, EPX, GPX3, ALOX12, IPCEF1, GSTA, OXR1, GPX6, AOX1, and PRNP. Therefore, a genetic OS background might underlie the complex pathogenesis of DKD in DM2 patients.

MeSH terms

  • Adult
  • Autoantigens / genetics
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / pathology*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Iodide Peroxidase / genetics
  • Iron-Binding Proteins / genetics
  • Male
  • Middle Aged
  • Osteopontin / genetics
  • Oxidative Stress / genetics*
  • Polymorphism, Single Nucleotide


  • Autoantigens
  • Iron-Binding Proteins
  • SPP1 protein, human
  • Osteopontin
  • TPO protein, human
  • Iodide Peroxidase