Abstract: TH-OR030

Circulating Serum miR-148b and let-7b Are Inherited in IgA Nephropathy (IgAN) Trios

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Serino, Grazia, IRCCS "S. de Bellis", Castellana Grotte (BA), Italy
  • Cox, Sharon N., University of Bari, Bari, Italy
  • Copetti, Massimiliano, IRCCS, San Giovanni Rotondo, Italy
  • Bisceglia, Luigi, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
  • Zaza, Gianluigi, University of Verona, Verona, Italy
  • Squarzoni, Isabella, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
  • Ferraresi, Martina, Nephrology, Dialysis and Transplantation, Turin, Italy
  • Biancone, Luigi, Department of Medical Science, Turin, Italy
  • Schena, Francesco Paolo, University of Bari, Bari, Italy
Background

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide characterized by aberrant O-glycosylation in the hinge region of IgA1. Our recent work demonstrates that serum levels of the combined miRNA biomarker, let-7b and miR-148b, appears to be a novel, reliable, and non-invasive test to predict the probability of having IgAN (Kidney International,89, 683-692; 2016). In this study our aim was to evaluate if the serum levels of the combined biomarker are heritable.

Methods

Serum miRNA was extracted using QIAzol Lysis Reagent and miRNeasy Mini Kit (Qiagen) according to the manufacturer’s protocol. Using quantitative real-time PCR, we detected the expression of circulating miRNAs (let-7b and miR-148b) in 90 trios that consists of one IgAN patient and their two parents. Heritability was estimated using the approach proposed in Rabe-Hesketh et al. (Biometrics, 64, 280-288, 2008) implemented in R package “gap”.

Results

We found that serum levels of the combined biomarker (let-7b and miR-148b) were elevated in the first-degree relatives of IgAN patients compared with healthy blood donors (IgAN 0.31±0.23; IgAN relatives 0.29±0.18; HBD -1.04±0.09). In addition, serum level of the combined biomarker did not differ between IgAN patients and their relatives (p=0.93). The estimated heritability (h2) of the serum biomarkers was 37,54% (95%CI: 13.57%-61,51%; p= 0.001) in crude (unudjasted) model. Age- and gender-adjusted heritability improved at 52.94% (95%CI=22.28%-83.59%, p=0.000356).

Conclusion

These results suggest that serum levels of the combined biomarker are, in part, genetically determined and may constitute a helpful tool for screening of relative at risk for IgAN development.

Funding

  • Government Support - Non-U.S.