The association between methylation levels of targeted genes and albuminuria in patients with early diabetic kidney disease

Ren Fail. 2017 Nov;39(1):597-601. doi: 10.1080/0886022X.2017.1358180.


Objective: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN.

Methods: We collected the clinical data of patients with type 2 diabetes mellitus. We measured spot urine albumin creatinine ratio to calculate albuminuria level. We divided patients into two groups based on albumin excretion as patients with (n = 69) and without DN (n = 27). We performed methylation profiling after bisulfite conversion by pyrosequencing method. The mean value of percent methylation level of each gene was calculated.

Results: We compared targeted genes (TIMP-2, AKR1B1, MMP-2, MMP-9, MYL9, SCL2A4, SCL2A1, SCL4A3) methylation levels and albuminuria. We found significant negative correlation between TIMP-2 and AKR1B1 gene methylation levels and albuminuria levels.

Conclusions: The present study provided evidence that hypomethylation of TIMP-2 and AKR1B1 genes can be associated with albuminuria in patients with early DN. We may speculate that the hypomethylation of TIMP-2 and AKR1B1 genes may be an early surrogate marker of DN.

Keywords: AKR1B1; TIMP-2; Type 2 diabetes; diabetic nephropathy; methylation; microalbuminuria.

Publication types

  • Comparative Study

MeSH terms

  • Albuminuria / diagnosis
  • Albuminuria / etiology
  • Albuminuria / urine*
  • Aldehyde Reductase / metabolism*
  • Biomarkers / urine
  • Creatinine / urine
  • DNA Methylation*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / urine*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / urine*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*


  • Biomarkers
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • Creatinine
  • AKR1B1 protein, human
  • Aldehyde Reductase

Grant support

The study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK-3001); The Grant number: 214S378.