Association of vitamin d receptor genotypes with calcium excretion in nephrolithiatic subjects in northern India

Abstract

Our objective was to investigate the association between the vitamin D receptor (VDR) allelic variants (Bsm I and Fok I) and nephrolithiasis in northern India. A total of 150 nephrolithiatic patients and 100 age and sex matched controls were enrolled for study. A 10 ml blood sample was obtained for biochemical analysis and DNA isolation. In addition, 24 h urine samples were obtained from each patient for the estimation of calcium and creatinine. PCR was performed for the Bsm I and Fok I VDR variants. The association between Bsm I and Fok I VDR polymorphism and nephrolithiasis was investigated after digestion with restriction enzymes (3 U). The product was analysed on 3% agarose gel for Bsm I and 15% polyacrylamide gel for Fok I allelic variants. We did not observe any significant differences in the prevalence of either the Bsm I or Fok I VDR genotypes between stone formers and controls. The B allele was found to be more prevalent in hypercalciuric patients compared to controls and nephrolithiatic subjects. The subjects with the bb genotype exhibited a higher calcium excretion than the BB genotype. Patients with the F allele were also found to excrete higher urinary calcium. VDR genotypes may be associated with increased calcium excretion in hypercalciuric nephrolithiatic subjects.

Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis

“…The high prevalence of Ff genotype in our population is accord to (25). In another study by (26) no association was observed with stone formation for VDR (Fok-I).…”

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

“…We thought that having a bb allele could be an independent risk factor for stone formation in normocalciuric infants, but in other studies from Turkey, Gunes et al 21 and Ö zkaya et al 24 found no significant association between BsmI VDR polymorphism and stone formation, nor did Relan et al 9 In this study, TaqI distribution differed significantly between the study and control groups, but ApaI did not. In contrast, Ozkaya et al 24 and Seyhan et al 25 found that the frequency of the ApaI AA genotype was significantly higher in the children with calcium nephrolithiasis than Gunes found no significant association of TaqI and ApaI with urolithiasis.…”

“…1,2,8 While knowledge is limited on how genetic factors mediate susceptibility to urolithiasis, one important factor is the function of the vitamin D receptor (VDR). Vitamin D plays a critical role in intestinal calcium absorption and renal calcium reabsorption, 9 and the VDR, a member of the steroid receptor family, mediates effects of the active metabolite 1,25-dihydroxyvitamin D3. 10 More than 60 polymorphisms have been reported in the VDR gene, 11 primarily related to such diseases as cancer, renal diseases, and diabetes.…”

“…13,14 These findings suggest that allelic variation of the VDR gene could be responsible for the genetic susceptibility associated with urolithiasis. Other studies have evaluated the association of the VDR gene with urolithiasis, hypercalciuria, and hypocitraturia, 9,12,15 but not for infantile urolithiasis. The aim of this study is to evaluate urolithiasis in the first year of life, its risk factors, demographic factors, and relationship with VDR gene polymorphisms.…”

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].…”