Abstract
The purpose of this study was to evaluate the impact of vitamin D receptor (VDR) gene polymorphisms on the status of active renal calcium stone formation. Male active renal calcium stone formers (ASF, final N = 106) with two episodes of stone relapse in the past 5 years were enrolled from December 2008 to April 2009. Controls (N = 109) were selected from age range- and gender-matched individuals who had no evidence or history of stone disease. Sequencing and single-strand conformational polymorphism were used to determine VDR polymorphisms in the patients and controls. Three polymorphisms were identified in the VDR gene: (1) start codon polymorphism (rs2228570T>C; p.M1T); (2) C/T polymorphism in the second intron (NT-029419.12: g.10416049C>T); (3) a silent polymorphism in exon 9 (rs731236T>C; p.I352I). Start codon polymorphism was the only one that was associated with the status of calcium stone formation (p < 0.05). We performed a complete coding genome analysis of VDR gene and observed that only start codon polymorphism was related to the status of active calcium stone formation.
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Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921
Bid HK, Chaudhary H, Mittal RD (2005) Association of vitamin-D and calcitonin receptor gene polymorphism in paediatric nephrolithiasis. Pediatr Nephrol 20:773–776
Chen WC, Chen HY, Lu HF, Hsu CD, Tsai FJ (2001) Association of the vitamin D receptor gene start codon Fok I polymorphism with calcium oxalate stone disease. BJU Int 87:168–171
Clubbe W (1874) Family disposition to urinary concretions. Lancet 1:823
Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1997) Family history and risk of kidney stones. J Am Soc Nephrol 8:1568–1573
Griffin DG (2004) A review of the heritability of idiopathic nephrolithiasis. J Clin Pathol 57:793–796
Harvey JA, Zobitz MM, Pak CY (1989) Bioavailability of citrate from two different preparations of potassium citrate. J Clin Pharmacol 29:338–341
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, Dominguez CE, Jurutka PW (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 13:325–349
Hess BT, Tiselius HG (2002) Physical–chemical process in kidney stone formation. In: Coe FL, Flavus MG (eds) Disorders of bone and mineral metabolism. Lippincott Williams & Wilkins, Philadelphia, pp 619–628
Jackman SV, Kibel AS, Ovuworie CA, Moore RG, Kavoussi LR, Jarrett TW (1999) Familial calcium stone disease: TaqI polymorphism and the vitamin D receptor. J Endourol Endourol Soc 13:313–316
Konwar R, Chattopadhyay N, Bid HK (2008) Genetic polymorphism and pathogenesis of benign prostatic hyperplasia. BJU Int 102:536–544
Li S, Yang MH, Zeng CA, Wu WL, Huang XF, Ji Y, Zeng JQ (2008) Association of vitamin D receptor gene polymorphisms in Chinese patients with generalized aggressive periodontitis. J Periodontal Res 43:360–363
Mossetti G, Rendina D, Viceconti R, Manno G, Guadagno V, Strazzullo P, Nunziata V (2004) The relationship of 3′ vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis. Nephrol Dial Transplant 19:2259–2265
Parks JH, Coe FL (1986) A urinary calcium-citrate index for the evaluation of nephrolithiasis. Kidney Int 30:85–90
Relan V, Khullar M, Singh SK, Sharma SK (2004) Association of vitamin D receptor genotypes with calcium excretion in nephrolithiatic subjects in northern India. Urol Res 32:236–240
Rendina D, Mossetti G, Viceconti R, Sorrentino M, Castaldo R, Manno G, Guadagno V, Strazzullo P, Nunziata V (2004) Association between vitamin D receptor gene polymorphisms and fasting idiopathic hypercalciuria in recurrent stone-forming patients. Urology 64:833–838
Ruggiero M, Pacini S, Amato M, Aterini S, Chiarugi V (1999) Association between vitamin D receptor gene polymorphism and nephrolithiasis. Miner Electrolyte Metab 25:185–190
Scott P, Ouimet D, Valiquette L, Guay G, Proulx Y, Trouve ML, Gagnon B, Bonnardeaux A (1999) Suggestive evidence for a susceptibility gene near the vitamin D receptor locus in idiopathic calcium stone formation. J Am Soc Nephrol 10:1007–1013
Shakhssalim N, Gilani KR, Parvin M, Torbati PM, Kashi AH, Azadvari M, Golestan B, Basiri A (2011) An assessment of parathyroid hormone, calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors. Urol Res 39:1–7
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156
Zmuda JM, Cauley JA, Ferrell RE (2000) Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 22:203–217
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This study was supported by grants from the Iranian Special Medical Centre (Charity Foundation for Special Diseases) and the Urology and Nephrology Research Centre (UNRC).
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Basiri, A., Shakhssalim, N., Houshmand, M. et al. Coding region analysis of vitamin D receptor gene and its association with active calcium stone disease. Urol Res 40, 35–40 (2012). https://doi.org/10.1007/s00240-011-0399-1
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DOI: https://doi.org/10.1007/s00240-011-0399-1