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Kidney Week

Abstract: FR-PO739

Global DNA Hypomethylation in Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Klawitter, Jelena, University of Colorado Denver, Aurora, Colorado, United States
  • You, Zhiying, UC Denver, Aurora, Colorado, United States
  • Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States
  • Hopp, Katharina, University of Colorado Denver, AMC, Aurora, Colorado, United States
  • Brosnahan, Godela M., University of Colorado Denver, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado , Aurora, Colorado, United States
  • Gitomer, Berenice Y., Div. Renal Diseases and Hypertension,, Aurora, Colorado, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) affects an estimated 600,000 individuals in the United States. We have previously demonstrated that the serum level of s-adenosyl methionine (SAM): s-adenosyl homocysteine (SAH), an indicator of cellular methylation potential, is decreased in ADPKD patients with normal to mildly decreased kidney function. As the alteration in the methylation potential may influence DNA methylation, we hypothesized that global DNA hypomethylation may occur in ADPKD.

Methods

Global DNA methylation status was assessed in DNA extracted from whole blood and from kidney tissue by measurement of 5-methylcytosine content by ELISA (Epigentek, Farmingdale, NY). Blood samples were obtained from 17 subjects with ADPKD and normal or near normal kidney function and 12 age- and sex-matched healthy control subjects. Kidney tissue was available from 2 ADPKD patients and 2 control subjects.

Results

Global DNA methylation was significantly lower in the ADPKD subjects compared to healthy subjects (Table 1). Similarly, global DNA methylation was lower in the ADPKD kidney tissue (2.54% vs 5.80%). Renal blood flow decreases early in the course of disease and we show that SAM:SAH (methylation potential) is significantly correlated with renal blood flow (r = 0.45, p = 0.02). These findings suggests that decrease in methylation potential may be an early event in ADPKD.

Conclusion

Global DNA hypomethylation is present in ADPKD both in peripheral blood cells and in kidney tissue. As DNA hypomethylation might play a role in disease progression, agents that increase global DNA methylation might have therapeutic potential in ADPKD.

Global DNA methylation in ADPKD and healthy subjects
ParameterADPKD (N =17)Healthy Controls (N=12)P
Age (years)41 ± 1145 ± 110.32
Male/Female9/86/60.14
eGFR (ml/min/1.73m^2)77 ± 27  
Height corrected total kidney volume (ml)616 ± 190  
% Methylated DNA (blood cells)1.1 ± 0.53.5 ± 2.0< 0.0001

data presented as mean and standard deviation

Funding

  • Private Foundation Support