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 (rs731236)and 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.
- Journal Article