Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis

BMC Medical Genetics volume 20, Article number: 193 (2019) Cite this article

Abstract

Background

The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous.

Methods

Meta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD).

Results

The VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms.

Conclusions

The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.

Peer Review reports

Introduction

In human skin, solar rays facilitate the formation of vitamin D3 from 7-dehydrocholesterol. The vitamin D3 undergoes two-step hydroxylation to form 25-hydroxy vitamin D3 (25-OHD3) and biologically active 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) [1]. Vitamin D receptor (VDR) is a ligand-activated transcriptional factor requiring 1,25(OH)2D for its activation [2]. The deficiency of 25OHD or VDR is reported to activate renin-angiotensin system resulting in high angiotensin II levels, which damage renal parenchyma leading to increased risk for renal disease [3]. Considering the pivotal role of VDR in maintaining normal renal function, a number of studies have explored the possibility of association of VDR gene polymorphisms with renal disease risk. Among VDR polymorphisms reported to date, ApaI, and TaqI are widely studied for their association with ESRD, NL and DN [4,5,6]. The ApaI variant (rs7975232), which results in A to C transition, is located in the intron 8 of VDR gene, while TaqI variant (rs731236), which results in T to C transition is located in exon 9 [7].

The rs7975232 (NG_008731.1:g.64978G > T) is an intronic variant predicted to influence splice site changes that might affect the translation of VDR. The frequency of this variant is high as evidenced by 734 and 16,751 homozygous mutants in 1000G and ExAC databases. The rs731236 (NG_008731.1:g.65058 T > C) variant is near the exon-intron boundary (GCTG/attg) and hence likely to influence splicing and thus might affect the translation of VDR. The frequency of this variant is lower than that of rs7975232 with 242 and 7505 homozygous mutants identified in 1000G and ExAC databases.

Importantly, genetic studies examining the role of TakI and ApaI polymorphisms in the pathogeneses of NL, DN and ESRD remained ambiguous [4,5,6, 8,9,10,11,12]. Considering the significance of VDR signaling in the protection against renal diseases and the ambiguity in the studies relating VDR gene polymorphism with the disease etiology, present meta-analysis comprising 2669 renal disease cases and 3342 controls was carried out to clarify the association of VDR gene TaqI and ApaI polymorphisms with nephrolithiasis, ESRD and diabetic nephropathy.

Methods

Data extraction

The literature retrieval was carried out using keywords: vitamin D receptor or VDR, renal disease, nephrolithiasis or urolithiasis, diabetic nephropathy, TaqI (rs731236) and ApaI (rs7975232) in PubMed, Medline and google scholar databases. All the free full texts were retrieved and wherever full text was not available, reprint request was sent to the corresponding author of the respective article. The criteria to include in the meta-analysis were: 1) availability of full text of the article, 2) inclusion of studies involving both cases and controls (either online or through reprint from the corresponding author), 3) availability of raw data on genotypes, and 4) restricting to studies published in only English language. The information related to each study such as first author, year of study, ethnic group or population studied, distribution of genotypes in cases and controls etc. was computed. The decision on the studies to be included in meta-analysis was taken by all the authors of this study.

Meta-analysis

The data computed in four columns wherein first two columns represent the number of variant alleles in cases and controls and last two columns represent the number of ancestral alleles in cases and controls. Log (odds ratio) or effect size and standard error (SE) are calculated based on these four column data. Based on these two parameters, variance (SE2), weight and 95% confidence interval of effect size were calculated. Cochrane Q test and I2 statistics were performed to test the heterogeneity in the association. The plot of 1/SE and Z-statistics was also used as an index to test heterogeneity. The publication bias was based on the rank correlation of SE and v. The fixed effect and random effect models were generated based on Mantel Haenszel and DerSimonian Lair’s methods, respectively. If no evidence of heterogeneity was found, fixed effect model was considered. If test heterogeneity was significant, random effect model was considered.

Results

Figure 1 depicts the data extraction process for the meta-analysis. Of the 16 case-control studies retrieved on the association of TaqI polymorphism with renal disease (Table 1), four studies showed deviation from Hardy-Weinberg equilibrium [7, 13,14,15]. Among the different population groups included in this meta-analysis, the largest being that of Turkish representing five case-control studies [16,17,18,19,20], two studies from India [21, 22] and one each from China [23], Ireland [24], Italy [25], Spain [26] and Croatia [27]. In total, the final meta-analysis was based on the data of 2777 cases and 3522 controls representing 16 case-control studies.

Fig. 1
figure 1

PRISMA flowchart showing the steps in meta-analysis data extraction

Full size image
Table 1 Distribution of VDR1 TaqI polymorphism in different case-control studies
Full size table

Cochrane Q-test (Q: 13.72, p = 0.54) and I2 (0.00) statistics showed no evidence of heterogeneity in association. Egger’s test revealed no evidence of publication bias (p = 0.14). The VDR TaqI C-allele, under allele contrast fixed effect model, was associated with renal diseases calculated collectively for DN, ESRD and NL (OR: 1.11, 95% CI: 1.03–1.20, p = 0.008). (Figure 2) As shown Table 2, subtype analysis revealed Taql C- allele to be associated with ESRD (OR: 1.17, 95% CI: 1.02–1.34, p = 0.03) (Fig. 2). Among the different ethnic groups, Turkish population showed strong association between VDR TaqI polymorphism and renal disease in allele contrast model (C vs. T, OR: 1.19, 95% CI: 1.01–1.42, p = 0.04). Sensitivity analysis revealed that omitting either of the studies had no effect on overall outcome of disease risk.

Fig. 2
figure 2

Meta-analysis of association studies on VDR TaqI polymorphism vs. risk for renal disease. Forest plot: The terms experimental and control groups corresponds to cases and controls. Number of variant alleles was considered as events with respect to total number of alleles tested. This meta-analysis was based on 16 case-control studies representing seven population groups. VDR TaqI polymorphism was shown to exert risk for renal disease both in fixed effect and random effect models. Funnel Diagram: It is depicting that no heterogeneity in association. Sensitivity analysis: Exclusion of any of the study is not influencing the result

Full size image
Table 2 Subgroup analysis showing disease-specific risk with VDR TaqI polymorphism
Full size table

Of the 13 case-control studies (2440 cases and 3279 controls) retrieved on the association of ApaI polymorphism with renal disease (Table 3), five studies deviated from Hardy-Weinberg equilibrium [7, 15, 19, 21, 28]. Among the studies in accordance with HWE equilibrium, 3 studies were from Turkey [16, 17, 20], two from China [14, 23], and one each from Ireland [24] and Iran [29]. Cochrane Q-test (Q: 17.01, p = 0.03) and I2 (48.3) statistics showed high-degree of heterogeneity in association. Egger’s test revealed no evidence of publication bias (p = 0.54). The fixed effect model showed positive association of VDR ApaI polymorphism with all the renal disease cases (C vs. A, OR: 1.10, 95% CI: 1.01–1.19), whereas, random effect model showed null association (OR: 1.05, 95% CI: 0.93–1.19) (Fig. 3). Sensitivity analysis for ApaI polymorphism revealed that the sources of heterogeneity are two studies i.e. Wang et al. and Tripathi et al. However, overall trend suggests ApaI variant as a risk factor for renal disease. As shown in Table 4, subgroup analysis revealed association of VDR ApaI polymorphism with ESRD (C vs. A, OR: 1.31, 95% CI: 1.15–1.50, p = 0.0001) and no association with NL and DN.

Table 3 Distribution of VDR1 ApaI polymorphism across different case-controls studies
Full size table
Fig. 3
figure 3

Meta-analysis of association studies on VDR ApaI polymorphism vs. risk for renal disease. Forest plot: The terms experimental and control groups correspond to cases and controls. Number of variant alleles were considered as events with respect to total number of alleles tested. This meta-analysis was based on 13 case-control studies representing 5 population groups. VDR ApaI polymorphism was shown to exert risk for renal disease only in fixed effect model, but not in random effect model. Funnel Diagram: It is depicting that two studies are contributing to heterogeneity. Sensitivity analysis: Excluding two studies is influencing the results

Full size image
Table 4 Subgroup analysis showing disease-specific risk with VDR ApaI polymorphism
Full size table

Discussion

Deficiency of vitamin D or defective activation of VDR by its ligand, 1,25-dihydroxy vitamin D results in secondary hyperparathyroidism, angiotensin II-mediated renal damage and renal disease pathogenesis [3]. On the other hand, VDR activation suppressed inflammatory cell infiltration and inhibited nuclear factor-κB activation [30]. Likewise, active vitamin D3 and lentivirus-mediated transforming growth factor-β (TGF-β) interference effectively reduced renal fibrosis in rat models [31]. These observations highlight the importance of VDR signaling in maintaining normal renal function. Accordingly, a number of studies have investigated the effects of polymorphisms in VDR gene on renal disease etiology. Among these, TaqI, and ApaI polymorphisms are widely studied [4,5,6]. However, there is a considerable ambiguity among these genetic studies, possibly stemming from sample size, ethnicity or gene-environmental interactions [4,5,6, 8,9,10,11,12]. To clarify whether TaqI and apaI polymorphisms have a role in renal disease pathogenesis, this meta-analysis comprising 2777 renal disease cases including DN, NL and ESRD and 3522 healthy controls was carried out. The present meta-analysis revealed an increased disease risk for subjects harboring TaqI C-allele under fixed and random effect models. Subgroup analysis based on type of renal disease showed that VDR TaqI polymorphism is associated with ESRD in allele contrast model, whereas no significant association was found between TaqI polymorphism and DN and NL. In the case of ApaI polymorphism, Apal C-allele was found to be linked to ESRD, but not with DM or NL under fixed effect model. Earlier, Yang et al. performed a meta-analysis on 1510 cases and 1812 controls and found no association of BsmI, FokI, TaqI, and ApaI polymorphisms of VDR with end-stage renal disease. Inclusion of more studies benefited the current meta-analysis.

The direct role of solar rays in the synthesis of vitamin D is well known. In human skin, solar rays facilitate the formation of vitamin D3 from 7-dehydrocholesterol, which is evident from the presence of higher mean serum vitamin D levels in summer than in winter [32]. Likewise, higher vitamin D levels were found in populations living in regions known to have longer durations of sun exposure [33].

Conclusions

This meta-analysis revealed the association of VDR TaqI and ApaI polymorphisms with ESRD risk. This is the first meta-analysis study to simultaneously evaluate the association of DN, NL and ESRD with renal disease risk. Ethnicity, sample size, gene-environmental interactions appear to be responsible for inconsistencies observed in the association studies examining VDR polymorphisms and renal diseases. The limitations of this meta-analysis include; exclusion of studies where raw data or full text were not accessible and one-to-one correlation between vitamin D3 profile and risk could not be established as no parallel studies were conducted.

Availability of data and materials

All data generated or analyzed during this study are included in this manuscript.

Abbreviations

1,25 (OH)2D3:

1,25-dihydroxyvitamin D3

25-OHD3:

25-hydroxy vitamin D3

DN:

diabetic nephropathy

ESRD:

end stage renal disease

NL:

nephrolithiasis

VDR:

vitamin D receptor

References

  1. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29.

    Article  CAS  Google Scholar 

  2. Ogunkolade BW, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K, North BV, Mannan N, McDermott MF, DeLuca HF, et al. Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes. 2002;51(7):2294–300.

    Article  CAS  Google Scholar 

  3. Chandel N, Ayasolla K, Wen H, Lan X, Haque S, Saleem MA, Malhotra A, Singhal PC. Vitamin D receptor deficit induces activation of renin angiotensin system via SIRT1 modulation in podocytes. Exp Mol Pathol. 2017;102(1):97–105.

    Article  CAS  Google Scholar 

  4. Yang L, Wu L, Fan Y, Ma J. Associations among four polymorphisms (BsmI, FokI, TaqI and ApaI) of vitamin D receptor gene and end-stage renal disease: a meta-analysis. Arch Med Res. 2015;46(1):1–7.

    Article  Google Scholar 

  5. Yang L, Wu L, Fan Y, Ma J. Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis. BMC Med Genet. 2017;18(1):95.

    Article  CAS  Google Scholar 

  6. Zhou TB, Jiang ZP, Huang MF. Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility. J Recept Signal Transduct Res. 2015;35(1):54–7.

    Article  Google Scholar 

  7. Nosratabadi R, Arababadi MK, Salehabad VA, Shamsizadeh A, Mahmoodi M, Sayadi AR, Kennedy D. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes. Int J Immunogenet. 2010;37(6):493–7.

    Article  CAS  Google Scholar 

  8. Liu W, Chen M, Li M, Ma H, Tong S, Lei Y, Qi L. Vitamin D receptor gene (VDR) polymorphisms and the urolithiasis risk: an updated meta-analysis based on 20 case-control studies. Urolithiasis. 2014;42(1):45–52.

    Article  Google Scholar 

  9. Zhang P, Nie W, Jiang H. Effects of vitamin D receptor polymorphisms on urolithiasis risk: a meta-analysis. BMC Med Genet. 2013;14:104.

    Article  CAS  Google Scholar 

  10. Yin F, Liu J, Fan MX, Zhou XL, Zhang XL. Association between the vitamin D receptor gene polymorphisms and diabetic nephropathy risk: a meta-analysis. Nephrology (Carlton). 2018;23(2):107–16.

    Article  CAS  Google Scholar 

  11. Liu Z, Liu L, Chen X, He W, Yu X. Associations study of vitamin D receptor gene polymorphisms with diabetic microvascular complications: a meta-analysis. Gene. 2014;546(1):6–10.

    Article  CAS  Google Scholar 

  12. Matana A, Popovic M, Torlak V, Punda A, Barbalic M, Zemunik T. Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97(21):e10834.

    Article  CAS  Google Scholar 

  13. Guha M, Bankura B, Ghosh S, Pattanayak AK, Ghosh S, Pal DK, Puri A, Kundu AK, Das M. Polymorphisms in CaSR and CLDN14 genes associated with increased risk of kidney stone disease in patients from the eastern part of India. PLoS One. 2015;10(6):e0130790.

    Article  Google Scholar 

  14. Han RDX, Su B, Yang W, Liu H, Song D. Association between TaqI, ApaI of vitamin D receptor gene polymorphism and type 2 diabetic nephropathy of the Han nationality in Kunming. Chin Med Herald. 2015;12(9):69–72.

    CAS  Google Scholar 

  15. Goknar N, Oktem F, Torun E, Gok O, Demir AD, Kucukkoc M, Kilic U. The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis. Ren Fail. 2016;38(4):545–51.

    Article  CAS  Google Scholar 

  16. Ozkaya O, Soylemezoglu O, Misirlioglu M, Gonen S, Buyan N, Hasanoglu E. Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children. Eur Urol. 2003;44(1):150–4.

    Article  Google Scholar 

  17. Gunes S, Bilen CY, Kara N, Asci R, Bagci H, Yilmaz AF. Vitamin D receptor gene polymorphisms in patients with urolithiasis. Urol Res. 2006;34(1):47–52.

    Article  CAS  Google Scholar 

  18. Seyhan S, Yavascaoglu I, Kilicarslan H, Dogan HS, Kordan Y. Association of vitamin D receptor gene Taq I polymorphism with recurrent urolithiasis in children. Int J Urol. 2007;14(12):1060–2.

    Article  CAS  Google Scholar 

  19. Aykan S, Tuken M, Gunes S, Akin Y, Ozturk M, Seyhan S, Yuruk E, Temiz MZ, Yilmaz AF, Nguyen DP. ApaL1 urokinase and Taq1 vitamin D receptor gene polymorphisms in first-stone formers, recurrent stone formers, and controls in a Caucasian population. Urolithiasis. 2016;44(2):109–15.

    Article  CAS  Google Scholar 

  20. Cakir OO, Yilmaz A, Demir E, Incekara K, Kose MO, Ersoy N. Association of the BsmI, ApaI, TaqI, Tru9I and FokI polymorphisms of the vitamin D receptor gene with nephrolithiasis in the Turkish population. Urol J. 2016;13(1):2509–18.

    PubMed  Google Scholar 

  21. Tripathi G, Sharma R, Sharma RK, Gupta SK, Sankhwar SN, Agrawal S. Vitamin D receptor genetic variants among patients with end-stage renal disease. Ren Fail. 2010;32(8):969–77.

    Article  CAS  Google Scholar 

  22. Mittal RD, Mishra DK, Srivastava P, Manchanda P, Bid HK, Kapoor R. Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis. Indian J Clin Biochem. 2010;25(2):119–26.

    Article  CAS  Google Scholar 

  23. Wang LY, Zhang P, Wang HF, Qin ZW, Wei KB, Lv XA. Association of vitamin D receptor gene polymorphisms with end-stage renal disease and the development of high-turnover renal osteodystrophy in a Chinese population. Genet Mol Res. 2016;15(2)

  24. Martin RJ, McKnight AJ, Patterson CC, Sadlier DM, Maxwell AP, Warren UKGSG. A rare haplotype of the vitamin D receptor gene is protective against diabetic nephropathy. Nephrol Dial Transplant. 2010;25(2):497–503.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Moyano MJ, Gomez de Tejada MJ, Garcia Lozano R, Moruno R, Ortega R, Marti V, Sanchez Palencia R, Miranda MJ, Palma A, Perez Cano R. Alterations in bone mineral metabolism in patients with calcium kidney stone disease and polymorphism of vitamin D receptor. Preliminary results. Nefrologia. 2007;27(6):694–703.

    CAS  PubMed  Google Scholar 

  27. Bucan K, Ivanisevic M, Zemunik T, Boraska V, Skrabic V, Vatavuk Z, Galetovic D, Znaor L. Retinopathy and nephropathy in type 1 diabetic patients--association with polymorphysms of vitamin D-receptor, TNF, Neuro-D and IL-1 receptor 1 genes. Coll Antropol. 2009;33(Suppl 2):99–105.

    CAS  PubMed  Google Scholar 

  28. Zhang H, Wang J, Yi B, Zhao Y, Liu Y, Zhang K, Cai X, Sun J, Huang L, Liao Q. BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population. Gene. 2012;495(2):183–8.

    Article  CAS  Google Scholar 

  29. Ghorbanihaghjo A, Argani H, Samadi N, Valizadeh S, Halajzadeh J, Yousefi B, Rashtchizadeh N. Relationship between vitamin D receptor gene FokI and ApaI polymorphisms and serum levels of fetuin-A, vitamin D, and parathyroid hormone in patients on hemodialysis. Iran J Kidney Dis. 2014;8(5):394–400.

    PubMed  Google Scholar 

  30. Singh PK, van den Berg PR, Long MD, Vreugdenhil A, Grieshober L, Ochs-Balcom HM, Wang J, Delcambre S, Heikkinen S, Carlberg C, et al. Integration of VDR genome wide binding and GWAS genetic variation data reveals co-occurrence of VDR and NF-kappaB binding that is linked to immune phenotypes. BMC Genomics. 2017;18(1):132.

    Article  Google Scholar 

  31. Tian Y, Lv G, Yang Y, Zhang Y, Yu R, Zhu J, Xiao L, Zhu J. Effects of vitamin D on renal fibrosis in diabetic nephropathy model rats. Int J Clin Exp Pathol. 2014;7(6):3028–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Cinar N, Harmanci A, Yildiz BO, Bayraktar M. Vitamin D status and seasonal changes in plasma concentrations of 25-hydroxyvitamin D in office workers in Ankara, Turkey. Eur J Intern Med. 2014;25(2):197–201.

    Article  CAS  Google Scholar 

  33. Leary PF, Zamfirova I, Au J, McCracken WH. Effect of latitude on vitamin D levels. J Am Osteopath Assoc. 2017;117(7):433–9.

    Article  Google Scholar 

Download references

Acknowledgments

Not applicable

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project No. RG-1439-74.

Funding Role: The funding body has provided the funds for data collection and analysis and has no role in design of the study, data interpretation and manuscript writing.

Author information

Authors and Affiliations

  1. Center of Excellence in Biotechnology Research, Department of Biochemistry, College of Science Building 5, King Saud University, Riyadh, 11451, Saudi Arabia

    Tajamul Hussain, Anwar Ahmed, Salman Alamery & Arif A. Mohammed

  2. Biochemical Genetics, Sandor Life Sciences Pvt. Ltd, Hyderabad, India

    Shaik M. Naushad

  3. Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia

    Salman Alamery, Mohamed O. Abdelkader & Nasser Abobakr Nasser Alkhrm

Authors
  1. Tajamul Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaik M. Naushad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anwar Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salman Alamery
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arif A. Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohamed O. Abdelkader
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nasser Abobakr Nasser Alkhrm
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TH conceived the study, participated in data analysis and manuscript writing, SMN participated in data analysis and manuscript writing, AA participated in data analysis, SA participated in data compilation and manuscript writing, AAM participated in data analysis and manuscript writing, MOA participated in data analysis. NANA participated in data compilation and manuscript writing. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Tajamul Hussain.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hussain, T., Naushad, S.M., Ahmed, A. et al. Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis. BMC Med Genet 20, 193 (2019). https://doi.org/10.1186/s12881-019-0932-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12881-019-0932-6

Keywords

BMC Medical Genetics

ISSN: 1471-2350

Contact us