Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis

Abstract

Objectives. Hypocitraturia is a risk factor for calcium nephrolithiasis. 1,25(OH) 2 D 3 influences renal citrate handling and enhances citraturia. The aim of this study was to evaluate the relationship between vitamin D receptor (VDR) allelic variant and urinary citrate excretion in recurrent stone formers (SF) patients. Design. Case-control study. Subjects. A total of 220 recurrent calcium oxalate SF patients and 114 healthy control (C) subjects were enrolled for this study. Subjects with urinary tract infections, hyperparathyroidism, cystinuria >70 lmol/24 h, gouty diathesis, renal tubular acidosis, renal failure, chronic diarrhoeal states, intake of thiazide diuretics, angiotensin-converting enzyme (ACE)-inhibitors, glucocorticoids or oestrogens were excluded. A standard constant diet was given for 7 days. The 24-h urinary citrate excretion and the active tubular reabsorption of filtered citrate (Rcit) were evaluated. Hypocitraturia was defined as a urinary citrate excretion lower than 1.7 mmol day )1 .Stone formers patients and C were genotyped for BsmI and TaqI VDR alleles. Contingency table chi-square tests were used to compare genotype frequencies in hypocitraturic SF patients, normocitraturic SF and C.Results. The prevalence of hypocitraturia in SF patients was 32.7% (72 of 200). Hypocitraturia in these patients resulted from excessive Rcit of a normal load of citrate. We found a different distribution (P < 0.05) of BsmI and TaqI VDR genotypes in hypocitraturic SF patients compared with normocitraturic SF and C. In particular, the prevalence of bb and TT VDR genotypes in hypocitraturic SF was significantly higher than in normocitraturic SF and C. Conclusions. These results point to a genetic association between BsmI and TaqI VDR polymorphisms and idiopathic hypocitraturia in calciumoxalate recurrent SF patients.

An Overview of Divalent Cation and Citrate Handling by the Kidney

“…Hypocitraturia is found in a third or more of renal stone patients, excluding those with primary or secondary (to medullary sponge kidney or other causes of nephrocalcinosis) dRTA [22], and recently an association has been demonstrated between polymorphisms of the vitamin D receptor and hypocitraturia [23]. However, as yet, no one has explored the potential for intrinsic changes in the transport activity of NaDC-1 itself.…”

Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

“…Several studies about common allelic variations in VDR in disorders of calcium metabolism, using Bsm I, Apa I, Taq I and Fok I restriction enzymes have been performed, but the results were controversial [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. While some studies disclosed an association between VDR polymorphism and bone mineral density (BMD) [12,13,14,15], others did not [16,17,18,19].…”

“…In addition, even if a specific VDR genotype does not provide evidence for a VDR defect per se, it could be a marker for the disease that could aid in the identification of a possible disease locus [12]. Evaluation of VDR polymorphisms among kidney stone formers, hypercalciuric or not, have shown distinct findings [16,20,21,22,23,24,25,26,27,28,29,30,31,32]. Some investigators found a positive association between polymorphic variations in VDR gene with risk or recurrence of stone formation [27,28,29] but other studies were negative [30,31].…”

The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis

“…18 Allelic variations are hypothesized to affect translational efficiency or stability in messenger RNA that may result in changes in VDR expression and further changes in target genes. 19 For this reason, several polymorphisms of the VDR gene were evaluated, especially four single nucleotide polymorphisms (SNP): ApaI, BsmI, TaqI, and Fox I. The SNPs evaluated in this study are ApaI, BsmI, and TaqI.…”