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Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers

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Abstract

Background

Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na+-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR rs731236and SLC13A2 rs11567842 allelic variants in the pathogenesis of hypocitraturia.

Methods

Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene–gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR).

Results

The prevalence of VDR TT and SLC13A2 GG genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38–7.60 for VDR TT vs. VDR tt and OR 4.06, 95 % CI 1.75–9.42 for SLC13A2 GG vs. SLC13A2 AA). MDR analysis indicated a significant interaction between VDR TT and SLC13A2 GG in hypocitraturic SF compared to C [OR 3.81 (2.11–6.88)]. These data are compatible with an epistatic interaction between the VDR TT and SLC13A2 GG genotypes with a significant impact on the magnitude of the effect (suppressive effect).

Conclusions

These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

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Authors and Affiliations

  1. Department of Clinical Medicine and Surgery, Federico II University of Naples, via Pansini 5, 80131, Naples, Italy

    Domenico Rendina, Riccardo Muscariello, Michele Schiano di Cola & Pasquale Strazzullo

  2. Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Italian National Research Council, Naples, Italy

    Gianpaolo De Filippo

  3. AP-HP, CHU Bicêtre, Service de Médecine des Adolescents, Le Kremlin-Bicêtre, France

    Fernando Gianfrancesco & Teresa Esposito

  4. IRCCS INM Neuromed, Pozzilli, IS, Italy

    Teresa Esposito

Authors
  1. Domenico Rendina
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  2. Gianpaolo De Filippo
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  3. Fernando Gianfrancesco
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  4. Riccardo Muscariello
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  5. Michele Schiano di Cola
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  6. Pasquale Strazzullo
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Correspondence to Domenico Rendina.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Rendina, D., De Filippo, G., Gianfrancesco, F. et al. Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers. J Nephrol 30, 411–418 (2017). https://doi.org/10.1007/s40620-016-0348-8

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  • DOI: https://doi.org/10.1007/s40620-016-0348-8

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