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.