Skip to main content

Advertisement

SpringerLink
Log in

Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study and comprehensive meta-analysis

  • Original Paper
  • Published:
Urolithiasis Aims and scope Submit manuscript

Abstract

Polymorphisms of vitamin D receptor (VDR) gene have been associated with risk of urolithiasis, but, with inconsistent results and lack data from Pakistani population. Therefore, after including our indigenous study data, a comprehensive meta-analysis was performed to provide an evidence-based estimate of any association between VDR polymorphisms and urolithiasis risk. A total of 483 Pakistani subjects, comprising 235 urolithiasis patients and 248 healthy controls, were genotyped for 6 VDR polymorphisms. Additionally, a systematic literature search with subsequent meta-analysis was conducted and pooled odds ratios (ORs) were used to determine the strength of any existent associations. Trial sequential analysis (TSA) was also performed. Results revealed no significant association of any VDR polymorphism and urolithiasis risk in indigenous Pakistani patients. However, meta-analysis of 29 relevant studies indicated that VDR FokI polymorphism significantly increased the risk of urolithiasis in allelic (f vs. F: OR = 1.13; 95% CI = 1.05–1.22; p ≤ 0.01) and recessive (ff vs. FF + Ff: OR = 1.20; 95% CI = 1.05–1.38; p = 0.01) models with no significant heterogeneity. No associations were evident for VDR ApaI, BsmI and TaqI polymorphic variants and urolithiasis risk after correction for multiple testing. Subgroup analysis by ethnicity suggested significant association for FokI variant among Asians. The TSA results demonstrated that the evidence reflecting association of FokI polymorphism and urolithiasis risk was sufficient and conclusive. In conclusion, this meta-analysis suggests that VDR FokI polymorphism is significantly associated with urolithiasis risk, especially in Asians, whereas ApaI, BsmI and TaqI polymorphisms are not associated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Pritchard JK, Cox NJ (2002) The allelic architecture of human disease genes: common disease-common variant or not? Hum Mol Genet 11(20):2417–2423

    Article  CAS  Google Scholar 

  2. Foulkes AS (2009) Applied statistical genetics with R: for population-based association studies. Use R!. Springer, New York

    Book  Google Scholar 

  3. Dampf Stone A, Batie SF, Sabir MS, Jacobs ET, Lee JH, Whitfield GK, Haussler MR, Jurutka PW (2015) Resveratrol potentiates vitamin D and nuclear receptor signaling. J Cell Biochem 116(6):1130–1143. https://doi.org/10.1002/jcb.25070

    Article  CAS  PubMed  Google Scholar 

  4. Haussler MR, Jurutka PW, Mizwicki M, Norman AW (2011) Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 25(4):543–559. https://doi.org/10.1016/j.beem.2011.05.010

    Article  CAS  PubMed  Google Scholar 

  5. Jacobs TP, Kaufman M, Jones G, Kumar R, Schlingmann K-P, Shapses S, Bilezikian JP (2014) A lifetime of hypercalcemia and hypercalciuria, finally explained. J Clin Endocrinol Metab 99(3):708–712. https://doi.org/10.1210/jc.2013-3802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367(6460):284–287. https://doi.org/10.1038/367284a0

    Article  CAS  PubMed  Google Scholar 

  7. 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(6):915–921. https://doi.org/10.1359/jbmr.1997.12.6.915

    Article  CAS  PubMed  Google Scholar 

  8. Uitterlinden AG, Fang Y, Van Meurs JBJ, Pols HAP, Van Leeuwen JPTM (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2):143–156. https://doi.org/10.1016/j.gene.2004.05.014

    Article  CAS  PubMed  Google Scholar 

  9. Li XQ, Tembe V, Horwitz GM, Bushinsky DA, Favus MJ (1993) Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption. J Clin Investig 91(2):661–667. https://doi.org/10.1172/jci116246

    Article  CAS  PubMed  Google Scholar 

  10. Scott P, Ouimet D, Valiquette L, Guay G, Proulx Y, Trouvé 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(5):1007–1013

    CAS  PubMed  Google Scholar 

  11. Rule AD, Bergstralh EJ, Melton LJ, Li X, Weaver AL, Lieske JC (2009) Kidney stones and the risk for chronic kidney disease. Clin J Am Soc Nephrol 4(4):804–811. https://doi.org/10.2215/CJN.05811108

    Article  PubMed  PubMed Central  Google Scholar 

  12. Scales CD, Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America P (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160–165. https://doi.org/10.1016/j.eururo.2012.03.052

    Article  PubMed  PubMed Central  Google Scholar 

  13. Germino G, Kirkali Z (2015) Urinary stone disease research challenges and opportunities meeting minutes. National Institute of Diabetes and Digestive and Kidney Diseases, NIH Campus, Bethesda, USA

  14. Goldfarb DS, Fischer ME, Keich Y, Goldberg J (2005) A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int 67(3):1053–1061. https://doi.org/10.1111/j.1523-1755.2005.00170.x

    Article  PubMed  Google Scholar 

  15. Goldfarb DS, Avery AR, Beara-Lasic L, Duncan GE, Goldberg J (2019) A twin study of genetic influences on nephrolithiasis in women and men. Kidney Int Rep 4(4):535–540. https://doi.org/10.1016/j.ekir.2018.11.017

    Article  PubMed  Google Scholar 

  16. Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, Wassner AJ, Nelson CP, Tasic V, Sayer JA, Hildebrandt F (2015) Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol 26(3):543–551. https://doi.org/10.1681/ASN.2014040388

    Article  CAS  PubMed  Google Scholar 

  17. Braun DA, Lawson JA, Gee HY, Halbritter J, Shril S, Tan W, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Fisher B, Spaneas L, Varner J, Sayer JA, Milosevic D, Baum M, Tasic V, Hildebrandt F (2016) Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol 11(4):664–672. https://doi.org/10.2215/CJN.07540715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Daga A, Majmundar AJ, Braun DA, Gee HY, Lawson JA, Shril S, Jobst-Schwan T, Vivante A, Schapiro D, Tan W, Warejko JK, Widmeier E, Nelson CP, Fathy HM, Gucev Z, Soliman NA, Hashmi S, Halbritter J, Halty M, Kari JA, El-Desoky S, Ferguson MA, Somers MJG, Traum AZ, Stein DR, Daouk GH, Rodig NM, Katz A, Hanna C, Schwaderer AL, Sayer JA, Wassner AJ, Mane S, Lifton RP, Milosevic D, Tasic V, Baum MA, Hildebrandt F (2018) Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int 93(1):204–213. https://doi.org/10.1016/j.kint.2017.06.025

    Article  CAS  PubMed  Google Scholar 

  19. Amar A, Majmundar AJ, Ullah I, Afzal A, Braun DA, Shril S, Daga A, Jobst-Schwan T, Ahmad M, Sayer JA, Gee HY, Halbritter J, Knöpfel T, Hernando N, Werner A, Wagner C, Khaliq S, Hildebrandt F (2019) Gene panel sequencing identifies a likely monogenic cause in 7% of 235 Pakistani families with nephrolithiasis. Hum Genet. https://doi.org/10.1007/s00439-019-01978-x

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sayer JA (2017) Progress in understanding the genetics of calcium-containing nephrolithiasis. J Am Soc Nephrol 28(3):748–759. https://doi.org/10.1681/ASN.2016050576

    Article  CAS  PubMed  Google Scholar 

  21. Civelek M, Lusis AJ (2014) Systems genetics approaches to understand complex traits. Nat Rev Genet 15(1):34–48. https://doi.org/10.1038/nrg3575

    Article  CAS  PubMed  Google Scholar 

  22. Lieske JC, Turner ST, Edeh SN, Smith JA, Kardia SLR (2014) Heritability of urinary traits that contribute to nephrolithiasis. Clin J Am Soc Nephrol 9(5):943–950. https://doi.org/10.2215/CJN.08210813

    Article  PubMed  PubMed Central  Google Scholar 

  23. Talati J, Khan F, Drago H, Lall E, Khan NZ, Talati A, Noordzij J (1997) Epidemiology of urolithiasis in Pakistan. The management of lithiasis. Developments in nephrology. Springer, Dordrecht, pp 21–33

  24. SaH Rizvi, SaA Naqvi, Hussain Z, Hashmi A, Hussain M, Zafar MN, Mehdi H, Khalid R (2002) The management of stone disease. BJU Int 89(s1):62–68. https://doi.org/10.1046/j.1465-5101.2001.134.x

    Article  Google Scholar 

  25. Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics 22(15):1928–1929. https://doi.org/10.1093/bioinformatics/btl268

    Article  CAS  PubMed  Google Scholar 

  26. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinform (Oxf, Engl) 21(2):263–265. https://doi.org/10.1093/bioinformatics/bth457

    Article  CAS  Google Scholar 

  27. Abid A, Ajaz S, Khan AR, Zehra F, Hasan AS, Sultan G, Mohsin R, Hashmi A, Niamatullah N, Rizvi SA-U-H, Mehdi SQ, Khaliq S (2016) Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis. Urol Oncol 34(9):419.e411–419.e412. https://doi.org/10.1016/j.urolonc.2016.04.005

    Article  CAS  Google Scholar 

  28. Deeks JJ, Higgins JPT (2010) Statistical algorithms in review manager 5. In: Statistical methods group of the Cochrane collaboration, pp 1–11

  29. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  Google Scholar 

  30. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  Google Scholar 

  31. R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/

    Google Scholar 

  32. 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(3):236–240. https://doi.org/10.1007/s00240-004-0414-x

    Article  CAS  PubMed  Google Scholar 

  33. Bid HK, Chaudhary H, Mittal RD (2005) Association of vitamin-D and calcitonin receptor gene polymorphism in paediatric nephrolithiasis. Pediatr Nephrol 20(6):773–776. https://doi.org/10.1007/s00467-005-1846-4

    Article  PubMed  Google Scholar 

  34. Bid HK, Kumar A, Kapoor R, Mittal RD (2005) Association of vitamin D receptor-gene (FokI) polymorphism with calcium oxalate nephrolithiasis. J Endourol 19(1):111–115. https://doi.org/10.1089/end.2005.19.111

    Article  PubMed  Google Scholar 

  35. Mittal RD, Mishra DK, Srivastava P, Manchanda P, Bid HK, Kapoor R (2010) Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis. Indian J Clin Biochem 25(2):119–126. https://doi.org/10.1007/s12291-010-0023-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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 13(4):313–316. https://doi.org/10.1089/end.1999.13.313

    Article  CAS  PubMed  Google Scholar 

  37. Ruggiero M, Pacini S, Amato M, Aterini S, Chiarugi V (1999) Association between vitamin D receptor gene polymorphism and nephrolithiasis. Miner Electrolyte Metab 25(3):185–190. https://doi.org/10.1159/000057443

    Article  CAS  PubMed  Google Scholar 

  38. Mª Jesús Moyano Franco MJGdTR (2007) Changes in bone mineral metabolism in patients with recurrent urolithiasis and vitamin D receptor gene polymorphisms. Preliminary results. Nefrol (Engl Ed) 27(6):694–703

    Google Scholar 

  39. 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(9):2259–2265. https://doi.org/10.1093/ndt/gfh273

    Article  CAS  PubMed  Google Scholar 

  40. 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(4):833–838. https://doi.org/10.1016/j.urology.2004.05.013

    Article  PubMed  Google Scholar 

  41. Mossetti G, Vuotto P, Rendina D, Numis FG, Viceconti R, Giordano F, Cioffi M, Scopacasa F, Nunziata V (2003) Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis. J Intern Med 253(2):194–200

    Article  CAS  Google Scholar 

  42. Rendina D, De Filippo G, Gianfrancesco F, Muscariello R, Schiano di Cola M, Strazzullo P, Esposito T (2017) Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers. J Nephrol 30(3):411–418. https://doi.org/10.1007/s40620-016-0348-8

    Article  CAS  PubMed  Google Scholar 

  43. Ozkaya O, Söylemezoğlu O, Misirlioğlu M, Gönen S, Buyan N, Hasanoğlu E (2003) Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children. Eur Urol 44(1):150–154

    Article  Google Scholar 

  44. Seyhan S, Yavascaoglu I, Kilicarslan H, Dogan HS, Kordan Y (2007) Association of vitamin D receptor gene TaqI polymorphism with recurrent urolithiasis in children. Int J Urol 14(12):1060–1062. https://doi.org/10.1111/j.1442-2042.2007.01899.x

    Article  CAS  PubMed  Google Scholar 

  45. Aykan S, Tuken M, Gunes S, Akin Y, Ozturk M, Seyhan S, Yuruk E, Temiz MZ, Yılmaz AF, Nguyen DP (2016) ApaL1 urokinase and Taq1 vitamin D receptor gene polymorphisms in first-stone formers, recurrent stone formers, and controls in a Caucasian population. Urolithiasis 44(2):109–115. https://doi.org/10.1007/s00240-015-0813-1

    Article  CAS  PubMed  Google Scholar 

  46. Cakir OO, Yilmaz A, Demir E, Incekara K, Kose MO, Ersoy N (2016) Association of the BsmI, ApaI, TaqI, Tru9I and FokI polymorphisms of the vitamin D receptor gene with nephrolithiasis in the Turkish population. Urol J 13(1):2509–2518

    PubMed  Google Scholar 

  47. Goknar N, Öktem F, Torun E, Gok O, Demir AD, Kucukkoc M, Kilic U (2016) The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis. Ren Fail 38(4):545–551. https://doi.org/10.3109/0886022X.2016.1148557

    Article  CAS  PubMed  Google Scholar 

  48. Gunes S, Bilen CY, Kara N, Asci R, Bagci H, Yilmaz AF (2006) Vitamin D receptor gene polymorphisms in patients with urolithiasis. Urol Res 34(1):47–52. https://doi.org/10.1007/s00240-005-0033-1

    Article  CAS  PubMed  Google Scholar 

  49. Subaşı B, Gökçe İ, Delil K, Alpay H (2017) Vitamin D receptor gene polymorphisms in children with kidney stone disease. Turk J Pediatr 59(4):404–409. https://doi.org/10.24953/turkjped.2017.04.006

    Article  PubMed  Google Scholar 

  50. Chen WC, Chen HY, Lu HF, Hsu CD, Tsai FJ (2001) Association of the vitamin D receptor gene start codon FokI polymorphism with calcium oxalate stone disease. BJU Int 87(3):168–171

    Article  CAS  Google Scholar 

  51. Shaogang W, Jihong L, Shaoqun H, Zhangqun Y (2003) Association of vitamin D receptor gene polymorphisms with calcium oxalate calculus disease. J Huazhong Univ Sci Technol [Med Sci] 23(1):38–41. https://doi.org/10.1007/BF02829458

    Article  Google Scholar 

  52. Seo IY, Park KW, Park SC, Lee SJ, Kim MS, Kim JJ, Rim JS (2004) Vitamin D receptor gene BsaM I polymorphism as genetic marker in patients with calcium stone. Korean J Urol 45(11):1143–1147

    Google Scholar 

  53. Nishijima S, Sugaya K, Naito A, Morozumi M, Hatano T, Ogawa Y (2002) Association of vitamin D receptor gene polymorphism with urolithiasis. J Urol 167(5):2188–2191

    Article  CAS  Google Scholar 

  54. Wang S, Wang X, Wu J, Lin Y, Chen H, Zheng X, Zhou C, Xie L (2012) Association of vitamin D receptor gene polymorphism and calcium urolithiasis in the Chinese Han population. Urol Res 40(4):277–284. https://doi.org/10.1007/s00240-011-0438-y

    Article  CAS  PubMed  Google Scholar 

  55. Chen WC, Chen HY, Hsu CD, Wu JY, Tsai FJ (2001) No association of vitamin D receptor gene BsmI polymorphisms with calcium oxalate stone formation. Mol Urol 5(1):7–10. https://doi.org/10.1089/109153601750124203

    Article  CAS  PubMed  Google Scholar 

  56. Liu C-C, Huang C-H, Wu W-J, Huang S-P, Chou Y-H, Li C-C, Chai C-Y, Wu M-T (2007) Association of vitamin D receptor (Fok-I) polymorphism with the clinical presentation of calcium urolithiasis. BJU Int 99(6):1534–1538. https://doi.org/10.1111/j.1464-410X.2007.06792.x

    Article  CAS  PubMed  Google Scholar 

  57. Seo IY, Kang I-H, Chae S-C, Park SC, Lee Y-J, Yang YS, Ryu SB, Rim JS (2010) Vitamin D receptor gene AlwI, FokI, ApaI, and TaqI polymorphisms in patients with urinary stone. Urology 75(4):923–927. https://doi.org/10.1016/j.urology.2009.10.006

    Article  PubMed  Google Scholar 

  58. Yang Z, Wang Q, Zhong JF, Li L (2018) Polymorphisms of the VDR gene in patients with nephrolithiasis in a Han Chinese population. Urolithiasis. https://doi.org/10.1007/s00240-018-1053-y

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y (2017) Epidemiology of stone disease across the world. World J Urol 35(9):1301–1320. https://doi.org/10.1007/s00345-017-2008-6

    Article  PubMed  Google Scholar 

  60. Lin Y, Mao Q, Zheng X, Chen H, Yang K, Xie L (2011) Vitamin D receptor genetic polymorphisms and the risk of urolithiasis: a meta-analysis. Urol Int 86(3):249–255. https://doi.org/10.1159/000323949

    Article  CAS  PubMed  Google Scholar 

  61. Zhang P, Nie W, Jiang H (2013) Effects of vitamin D receptor polymorphisms on urolithiasis risk: a meta-analysis. BMC Med Genet 14:104. https://doi.org/10.1186/1471-2350-14-104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liu W, Chen M, Li M, Ma H, Tong S, Lei Y, Qi L (2014) Vitamin D receptor gene (VDR) polymorphisms and the urolithiasis risk: an updated meta-analysis based on 20 case-control studies. Urolithiasis 42(1):45–52. https://doi.org/10.1007/s00240-013-0619-y

    Article  CAS  PubMed  Google Scholar 

  63. Zhou T-B, Jiang Z-P, Li A-H, Ju L (2015) Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis susceptibility. J Recept Signal Transduct Res 35(2):107–114. https://doi.org/10.3109/10799893.2014.936459

    Article  CAS  PubMed  Google Scholar 

  64. Hu SQ, Liu JH, Wang SG, Cao ZG, Wu W (2004) Relationship between vitamin D receptor allele polymorphism and calcium oxalate stone disease. Chin J Urol 25(3):155–158

    CAS  Google Scholar 

  65. Wang Q, Qian B, Ding G, Zheng L (2009) Vitamin D receptor gene polymorphisms in Chinese uygur patients with urolithiasis in south Xinjian. J Pract Med 25(17):2805–2807

    CAS  Google Scholar 

  66. Ruan L, Li Z, Zheng R, Huang W, Shi G, Li G, Li S, Luo B (2012) Relationship between vitamin D receptor FokI polymorphism and calcium oxalate stone disease in Guangzhou Chinese patients. Guangdong Medical Journal 33(1):84–85

    CAS  Google Scholar 

  67. Aji K, Song G-L, Yasen A, Azad B, Tursun H (2012) Association of vitamin D receptor gene polymorphisms with urolithiasis in Uyghur children from southern Xinjiang, China. Zhongguo Dang Dai Er Ke Za Zhi 14(12):956–959

    CAS  PubMed  Google Scholar 

  68. Basiri A, Shakhssalim N, Houshmand M, Kashi AH, Azadvari M, Golestan B, Mohammadi Pargoo E, Pakmanesh H (2012) Coding region analysis of vitamin D receptor gene and its association with active calcium stone disease. Urol Res 40(1):35–40. https://doi.org/10.1007/s00240-011-0399-1

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank patients who participated in the study and hospital staff who facilitated the research team in data and sample collection. We also acknowledge the facilities and support provided by university staff.

Funding

This study was funded by Higher Education Commission, Pakistan (Grant no. NRPU#1987).

Author information

Authors and Affiliations

  1. Department of Human Genetics and Molecular Biology, University of Health Sciences, Khayaban-e-Jamia Punjab, Lahore, 54600, Pakistan

    Ali Amar, Ayesha Afzal, Madiha Shakoor & Shagufta Khaliq

  2. Department of Urology, Sheikh Zayed Medical College Hospital, Rahim Yar Khan, Pakistan

    Syed Atif Hussain

  3. Department of Urology, Fatima Jinnah Medical University, Lahore, Pakistan

    Athar Hameed

  4. Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, Pakistan

    Abdul Rafay Khan & Aiysha Abid

Authors
  1. Ali Amar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayesha Afzal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Syed Atif Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Athar Hameed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdul Rafay Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Madiha Shakoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aiysha Abid
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shagufta Khaliq
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shagufta Khaliq.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethical Review Committee for Medical and Biomedical Research, University of Health Sciences, Lahore) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 2889 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amar, A., Afzal, A., Hussain, S.A. et al. Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study and comprehensive meta-analysis. Urolithiasis 48, 385–401 (2020). https://doi.org/10.1007/s00240-019-01157-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-019-01157-7

Keywords

Search

Navigation