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Abstract: TH-PO204

The Genetic Background Predicts the Kind of Renal Damage and Fibrosis Progression in Diabetic Patients

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Pontrelli, Paola, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Cinefra, Claudia, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Conserva, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Rossini, M., Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Pesce, Francesco, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
  • Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
Background

Diabetic Nephropathy (DN) is the major causes of end-stage renal failure; renal damage in the diabetic patient can be real DN or non-diabetic renal disease (NDRD). We demonstrated that a characteristic feature only of real DN is an increase in Lys63-ubiquitination (PMID: 27881486; 29806072; 31388051; 34068941). The goal of this project was to identify single nucleotide polymorphisms (SNPs), associated to genes involved in Lys63 ubiquitination, able to predict the different kind of renal damage and the progression of kidney disease in diabetic patients.

Methods

We selected 10 HapMap SNPs within coding and regulatory sequences both of miR27b-3p and miR1228-3p , all involved in Lys63 ubiquitination, in order to evaluate their diagnostic and prognostic potential. 203 patients were enrolled in this study, in particular we included: diabetic patients with: i) DN, ii) NDRD, iii) without clinical signs of impaired renal function (T2D), iv) with coexistence of both conditions (ND+NDRD); non-diabetic patients with glomerulonephritis (CKD) or without renal damage (CTRL).

Results

The analyzed SNPs showed a different genotype frequency among all the patients classes. Interestingly, SNPs rs47, rs475, rs474, rs38 showed a statistically significant difference in genotypes frequency comparing DN patients with CEU Population (p<0.04, 0.05, 0.002, 0.001 respectively) and a control cohort enclosing CTRL and T2D (p<0.02, 0.05, 0.001, 0.04 respectively). SNPs rs76, rs107, rs23 genotypes frequency was statistically different among DN patients and the control cohort (p<0.001). The genotype frequencies of the SNPs rs107 (p<0.01) and rs78 (p<0.04) resulted significantly related to tubular fibrosis in DN patients, while the SNPs rs47 (p<0.03) and rs76 (p<0.02) to the glomerular one. In order to evaluate the diagnostic power of the identified SNPs, we used a logistic regression model, and we observed that the SNP rs107, adjusted for age, sex, eGFR and glycaemic index, discriminate DN from NDRD (p<0.05; OR=1.002-1.008; 95% CI).

Conclusion

Our data demonstrated that the allelic forms of the analyzed SNPs are related to the different kind of renal damage in diabetic patients. Their prognostic and diagnostic potential could represent the starting point to create a new non-invasive diagnosis system based on clinical and genotyping data.