http://informahealthcare.com/rst ISSN: 1079-9893 (print), 1532-4281 (electronic) J Recept Signal Transduct Res, Early Online: 1–5 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/10799893.2014.936462
RESEARCH ARTICLE
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Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients Tian-Biao Zhou, Zong-Pei Jiang, Miao-Fang Huang, and Rui Zhang Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Abstract
Keywords
Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.
Gene polymorphism, meta-analysis, nephrolithiasis, urine calcium level, vitamin D receptor
Introduction Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation and control of other hormonal systems (1). The vitamin D receptor (VDR) is an endocrine nuclear receptor for 1a,25-dihydroxyvitamin D3 (2). There have been several polymorphisms named according to the restriction sites, such as VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236). BsmI, FokI, ApaI and TaqI gene polymorphisms of VDR gene are regarded as reliable markers of disturbed vitamin D signaling pathway (3). VDR gene polymorphisms have been reported to influence susceptibility to some diseases (4–8). Nephrolithiasis is a multifactorial disease, and it is caused by environmental, hormonal and genetic factors (9). Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system, and it remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary (10). However, hypercalciuric and normocalciuric are two statuses of patients with
Address for correspondence: Tian-Biao Zhou, Department of Nephrology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China. Tel: +8613602424386. E-mail: [email protected], [email protected]
History Received 24 May 2014 Accepted 11 June 2014 Published online 7 July 2014
nephrolithiasis. Current evidence indicates that gene polymorphism of some genes are associated with the urine calcium level in nephrolithiasis patients. Gene polymorphism factor has been reported to be an important factor which is associated with the urine calcium level in nephrolithiasis patients. Most of the epidemiologic investigations studying the relationship between VDR gene polymorphism and the urine calcium level in nephrolithiasis patients were conducted in the past decades. However, the available evidence is weak, due to sparseness of data or disagreements among the reported investigations. The evidence from meta-analysis might be powerful compared with the individual investigation. This meta-analysis was performed to investigate whether the VDR gene polymorphism was associated with the urine calcium level in nephrolithiasis patients.
Materials and methods Search strategy for the relationship between vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the urine calcium level in nephrolithiasis patients The relevant studies were searched from the electronic databases of PubMed, and Cochrane Library on 1 April 2014. The retrieval strategy of ‘‘(vitamin D receptor OR VDR) AND (nephrolithiasis OR calcium kidney stones OR urolithiasis OR stone-Forming)’’ was entered into these
2
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–5
databases. The additional reports were identified through references cited in recruited articles.
Results
Inclusion and exclusion criteria
Four studies (15-18) reporting the relationship between VDR BsmI, Fok1, TaqI or ApaI gene polymorphism and the urine calcium level in nephrolithiasis patients were recruited into this meta-analysis (Table 1). The data of our interest were extracted (Table 1). Two studies were for BsmI (rs1544410) gene polymorphism, two studies were for Fok1 (rs2228570) gene polymorphism, one study was for VDR TaqI (rs731236) gene polymorphism and one study was for ApaI (rs7975232) gene polymorphism.
Inclusion criteria (1) The outcome had to be nephrolithiasis, (2) there had to be at least two comparison groups (hypercalciuric group versus normocalciuric group) and (3) investigation should provide the data of VDR BsmI, Fok1, TaqI and ApaI genotype distribution.
Study characteristics
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
Exclusion criteria (1) Review articles and editorials, (2) case reports, (3) preliminary result not on VDR BsmI, Fok1, TaqI and ApaI gene polymorphism or outcome, (4) investigating the role VDR gene expression to disease and (5) if multiple publications for the same data from the same study group occurred, we only recruited the later paper into our final analysis. Data extraction and synthesis The following information from each eligible study was extracted independently by two investigators: first author’s surname, year of publication, location of the study performed, control source of the control group and the number of cases and controls for VDR genotypes. The results were compared and disagreement was resolved by discussion. Statistical analysis Cochrane Review Manager Version 5 (RevMan, Version 5, Oxford, UK) was used to calculate the available data from each study. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the p value of heterogeneity test was 50.1 (11,12). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. p50.05 was required for the pooled OR to be statistically significant (13,14). I2 was used to test the heterogeneity among the included studies.
Association of VDR BsmI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, we found that VDR BsmI bb genotype was associated with the urine calcium level in nephrolithiasis patients, but B allele, and BB genotype not (bb genotype: OR ¼ 1.75, 95% CI: 1.01–3.02, p ¼ 0.05; B allele: OR ¼ 0.83, 95% CI: 0.57–1.21, p ¼ 0.34; BB genotype: OR ¼ 1.36, 95% CI: 0.66–2.78, p ¼ 0.40; Figure 1 and Table 2). Association of VDR Fok1 gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, we found that VDR Fok1 FF genotype was associated with the urine calcium level in nephrolithiasis patients, but f allele, and ff genotype not (FF genotype: OR ¼ 1.87, 95% CI: 1.09–3.22, p ¼ 0.02; f allele: OR ¼ 0.81, 95% CI: 0.57–1.16, p ¼ 0.26; ff genotype: OR ¼ 1.59, 95% CI: 0.61–4.12, p ¼ 0.34; Figure 2 and Table 2). Association of VDR TaqI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, VDR TaqI t allele, tt genotype and TT genotype were not associated with the urine calcium level in nephrolithiasis patients (t allele: OR ¼ 0.87, 95% CI: 0.49– 1.55, p ¼ 0.64; tt genotype: OR ¼ 0.69, 95% CI: 0.13–3.60, p ¼ 0.66; TT genotype: OR ¼ 1.17, 95% CI: 0.55–2.49, p ¼ 0.69; Figure 3 and Table 2).
Table 1. Characteristics of the studies evaluating the effects of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism on the urine calcium level in nephrolithiasis patients. Case Gene sites BsmI
Fok1
Control
Author, Year
Ethnicity
Country/subgroup
BB
Bb
bb
Total
BB
Bb
bb
Total
Ruggiero, 1999 Ferreira, 2010
Caucasian Brazilian
Italy Brazil
2 18
6 39
4 43
12 100
2 14
6 60
7 27
15 101
ff
Ff
FF
Total
ff
Ff
FF
Total
15 1
36 28
47 11
98 40
6 1
32 70
19 14
57 85
tt
Tt
TT
Total
tt
Tt
TT
Total
2
20
18
40
6
44
35
85
AA
Aa
aa
Total
AA
Aa
aa
Total
17
20
3
40
26
51
8
85
Vezzoli, 2002 Mittal, 2010
Caucasian Asian
Italy India
TaqI
Mittal, 2010
Asian
India
ApaI
Mittal, 2010
Asian
India
Association of VDR with urine calcium level
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
DOI: 10.3109/10799893.2014.936462
3
Figure 1. Association of VDR BsmI gene polymorphism with the urine calcium level in nephrolithiasis patients.
Table 2. Meta analysis of the association of VDR BsmI, Fok1, TaqI with the urine calcium level in nephrolithiasis patients. Genetic contrasts BsmI B versus b BB versus Bb + bb bb versus BB + Bb Fok1 f versus F ff versus Ff + FF FF versus Ff + ff TaqI t versus T tt versus Tt + TT TT versus Tt + tt ApaI A versus a AA versus Aa + aa aa versus AA + Aa
Studies Q test Model number p value selected
OR (95% CI)
p Value
2 2 2
0.31 0.97 0.13
Fixed 0.83(0.57, 1.21) 0.34 Fixed 1.36(0.66, 2.78) 0.40 Fixed 1.75(1.01, 3.02) 0.05
2 2 2
0.98 0.82 0.94
Fixed 0.81(0.57, 1.16) 0.26 Fixed 1.59(0.61, 4.12) 0.34 Fixed 1.87(1.09, 3.22) 0.02
1 1 1
– – –
Fixed 0.87(0.49, 1.55) 0.64 Fixed 0.69(0.13, 3.60) 0.66 Fixed 1.17(0.55, 2.49) 0.69
1 1 1
– – –
Fixed 1.35(0.77, 2.36) 0.29 Fixed 1.68(0.77, 3.65) 0.19 Fixed 0.78(0.20, 3.11) 0.73
Association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, the association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients was not found (A allele: OR ¼ 1.35, 95% CI: 0.77– 2.36, p ¼ 0.29; AA genotype: OR ¼ 1.68, 95% CI: 0.77–3.65, p ¼ 0.19; aa genotype: OR ¼ 0.78, 95% CI: 0.20–3.11, p ¼ 0.73; Figure 4 and Table 2).
Discussion In this meta-analysis for VDR, BsmI bb genotype was associated with the urine calcium level in nephrolithiasis patients, but the B allele and BB genotype was not associated. There were only two included studies for this meta-analysis, and the results might be less robust to some extent. More studies for the association between VDR BsmI gene polymorphism and the urine calcium level in nephrolithiasis patients should be performed in the future. In this meta-analysis, there were two included studies for VDR Fok1 in this meta-analysis, and the results might be slightly robust to some extent. VDR Fok1 FF genotype was associated with the urine calcium level in nephrolithiasis patients, but f allele, and ff genotype not. More studies for the association between VDR Fok1 gene polymorphism and the urine calcium level in nephrolithiasis patients should be performed in the future. In this meta-analysis, VDR TaqI t allele, tt genotype and TT genotype were not associated with the urine calcium level in nephrolithiasis patients. However, there was one included study in this meta-analysis. The results from this metaanalysis should be confirmed in the future. In this meta-analysis, VDR ApaI A allele, AA genotype and aa genotype were not associated with the urine calcium level in nephrolithiasis patients. There was only one recruited study in this meta-analysis. More studies should be conducted in the future.
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T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–5
Figure 2. Association of VDR Fok1 gene polymorphism with the urine calcium level in nephrolithiasis patients.
Figure 3. Association of VDR TaqI gene polymorphism with the urine calcium level in nephrolithiasis patients.
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
DOI: 10.3109/10799893.2014.936462
Association of VDR with urine calcium level
5
Figure 4. Association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients.
There was no any meta-analysis to study the association of VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the urine calcium level in nephrolithiasis patients using meta-analysis method. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, the number of included studies was small. The conclusion might be less robust, and more studies should be performed in the future. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.
Declaration of interest The authors declare no competing interests. This study was supported by the sub-item of 985 Project Foundation of Sun Yat-Sen (The Hundred Talents Program Foundation; No. 88000-3311300).
References 1. Adamczyk A, Stolarz-Skrzypek K, Wesolowska A, et al. Vitamin D and vitamin D receptor activators in treatment of hypertension and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets 2014. (Epub ahead of print). 2. Belorusova AY, Eberhardt J, Potier N, et al. Structural insights into the molecular mechanism of Vitamin D Receptor activation by lithocholic acid involving a new mode of ligand recognition. J Med Chem 2014;57:4710–9. 3. Santoro D, Gagliostro G, Alibrandi A, et al. Vitamin D receptor gene polymorphism and left ventricular hypertrophy in chronic kidney disease. Nutrients 2014;6:1029–37.
4. Qin WH, Wang HX, Qiu JL, et al. A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with the risk of type 1 diabetes mellitus. J Recept Signal Transduct Res 2014. (Epub ahead of print). 5. Ou C, Zhao HL, Zhu B, et al. Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis. J Recept Signal Transduct Res 2014. (Epub ahead of print). 6. Colombini A, Brayda-Bruno M, Lombardi G, et al. FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: a casecontrol study. PLoS One 2014;9:e97027. 7. Zhou TB, Jiang ZP, Lin ZJ, et al. Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus. J Recept Signal Transduct Res 2014. (Epub ahead of print). 8. Zhu B, Zhao HL, Ou C, et al. Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus. J Recept Signal Transduct Res 2014. (Epub ahead of print). 9. Kan WC, Chou YH, Chiu SJ, et al. Study of the association between ITPKC genetic polymorphisms and calcium nephrolithiasis. Biomed Res Int 2014;2014:397826. 10. Aggarwal KP, Narula S, Kakkar M, et al. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed Res Int 2013;2013: 292953. 11. Zhou TB, Yin SS. Association of matrix metalloproteinase-9 level with the risk of renal involvement for Henoch-Schonlein purpura in children. Ren Fail 2013;35:425–9. 12. Zhou TB, Yin SS, Jiang ZP. Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease. J Recept Signal Transduct Res 2013;33: 325–31. 13. Liu G, Zhou TB, Jiang Z, et al. Relationship between PPARgamma Pro12Ala gene polymorphism and type 2 diabetic nephropathy risk in Asian population: results from a meta-analysis. J Recept Signal Transduct Res 2014;34:131–6. 14. Zhou TB, Guo XF, Yin SS. Association of peroxisome proliferatoractivated receptor gamma Pro12Ala gene polymorphism with type 2 diabetic nephropathy risk in Caucasian population. J Recept Signal Transduct Res 2014;34:180–4.
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Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
15. Ruggiero M, Pacini S, Amato M, et al. Association between vitamin D receptor gene polymorphism and nephrolithiasis.Miner Electrolyte Metab 1999;25:185–90. 16. Ferreira LG, Pereira AC, Heilberg IP. Vitamin D receptor and calcium-sensing receptor gene polymorphisms in hypercalciuric stone-forming patients. Nephron Clin Pract 2010;114:c135–44.
J Recept Signal Transduct Res, Early Online: 1–5
17. Vezzoli G, Soldati L, Proverbio MC, et al. Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones. J Nephrol 2002;15:158–64. 18. Mittal RD, Mishra DK, Srivastava P, et al. Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis. Indian J Clin Biochem 2010;25:119–26.
RESEARCH ARTICLE
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients Tian-Biao Zhou, Zong-Pei Jiang, Miao-Fang Huang, and Rui Zhang Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Abstract
Keywords
Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.
Gene polymorphism, meta-analysis, nephrolithiasis, urine calcium level, vitamin D receptor
Introduction Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation and control of other hormonal systems (1). The vitamin D receptor (VDR) is an endocrine nuclear receptor for 1a,25-dihydroxyvitamin D3 (2). There have been several polymorphisms named according to the restriction sites, such as VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236). BsmI, FokI, ApaI and TaqI gene polymorphisms of VDR gene are regarded as reliable markers of disturbed vitamin D signaling pathway (3). VDR gene polymorphisms have been reported to influence susceptibility to some diseases (4–8). Nephrolithiasis is a multifactorial disease, and it is caused by environmental, hormonal and genetic factors (9). Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system, and it remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary (10). However, hypercalciuric and normocalciuric are two statuses of patients with
Address for correspondence: Tian-Biao Zhou, Department of Nephrology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China. Tel: +8613602424386. E-mail: [email protected], [email protected]
History Received 24 May 2014 Accepted 11 June 2014 Published online 7 July 2014
nephrolithiasis. Current evidence indicates that gene polymorphism of some genes are associated with the urine calcium level in nephrolithiasis patients. Gene polymorphism factor has been reported to be an important factor which is associated with the urine calcium level in nephrolithiasis patients. Most of the epidemiologic investigations studying the relationship between VDR gene polymorphism and the urine calcium level in nephrolithiasis patients were conducted in the past decades. However, the available evidence is weak, due to sparseness of data or disagreements among the reported investigations. The evidence from meta-analysis might be powerful compared with the individual investigation. This meta-analysis was performed to investigate whether the VDR gene polymorphism was associated with the urine calcium level in nephrolithiasis patients.
Materials and methods Search strategy for the relationship between vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the urine calcium level in nephrolithiasis patients The relevant studies were searched from the electronic databases of PubMed, and Cochrane Library on 1 April 2014. The retrieval strategy of ‘‘(vitamin D receptor OR VDR) AND (nephrolithiasis OR calcium kidney stones OR urolithiasis OR stone-Forming)’’ was entered into these
2
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–5
databases. The additional reports were identified through references cited in recruited articles.
Results
Inclusion and exclusion criteria
Four studies (15-18) reporting the relationship between VDR BsmI, Fok1, TaqI or ApaI gene polymorphism and the urine calcium level in nephrolithiasis patients were recruited into this meta-analysis (Table 1). The data of our interest were extracted (Table 1). Two studies were for BsmI (rs1544410) gene polymorphism, two studies were for Fok1 (rs2228570) gene polymorphism, one study was for VDR TaqI (rs731236) gene polymorphism and one study was for ApaI (rs7975232) gene polymorphism.
Inclusion criteria (1) The outcome had to be nephrolithiasis, (2) there had to be at least two comparison groups (hypercalciuric group versus normocalciuric group) and (3) investigation should provide the data of VDR BsmI, Fok1, TaqI and ApaI genotype distribution.
Study characteristics
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Exclusion criteria (1) Review articles and editorials, (2) case reports, (3) preliminary result not on VDR BsmI, Fok1, TaqI and ApaI gene polymorphism or outcome, (4) investigating the role VDR gene expression to disease and (5) if multiple publications for the same data from the same study group occurred, we only recruited the later paper into our final analysis. Data extraction and synthesis The following information from each eligible study was extracted independently by two investigators: first author’s surname, year of publication, location of the study performed, control source of the control group and the number of cases and controls for VDR genotypes. The results were compared and disagreement was resolved by discussion. Statistical analysis Cochrane Review Manager Version 5 (RevMan, Version 5, Oxford, UK) was used to calculate the available data from each study. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the p value of heterogeneity test was 50.1 (11,12). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. p50.05 was required for the pooled OR to be statistically significant (13,14). I2 was used to test the heterogeneity among the included studies.
Association of VDR BsmI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, we found that VDR BsmI bb genotype was associated with the urine calcium level in nephrolithiasis patients, but B allele, and BB genotype not (bb genotype: OR ¼ 1.75, 95% CI: 1.01–3.02, p ¼ 0.05; B allele: OR ¼ 0.83, 95% CI: 0.57–1.21, p ¼ 0.34; BB genotype: OR ¼ 1.36, 95% CI: 0.66–2.78, p ¼ 0.40; Figure 1 and Table 2). Association of VDR Fok1 gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, we found that VDR Fok1 FF genotype was associated with the urine calcium level in nephrolithiasis patients, but f allele, and ff genotype not (FF genotype: OR ¼ 1.87, 95% CI: 1.09–3.22, p ¼ 0.02; f allele: OR ¼ 0.81, 95% CI: 0.57–1.16, p ¼ 0.26; ff genotype: OR ¼ 1.59, 95% CI: 0.61–4.12, p ¼ 0.34; Figure 2 and Table 2). Association of VDR TaqI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, VDR TaqI t allele, tt genotype and TT genotype were not associated with the urine calcium level in nephrolithiasis patients (t allele: OR ¼ 0.87, 95% CI: 0.49– 1.55, p ¼ 0.64; tt genotype: OR ¼ 0.69, 95% CI: 0.13–3.60, p ¼ 0.66; TT genotype: OR ¼ 1.17, 95% CI: 0.55–2.49, p ¼ 0.69; Figure 3 and Table 2).
Table 1. Characteristics of the studies evaluating the effects of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism on the urine calcium level in nephrolithiasis patients. Case Gene sites BsmI
Fok1
Control
Author, Year
Ethnicity
Country/subgroup
BB
Bb
bb
Total
BB
Bb
bb
Total
Ruggiero, 1999 Ferreira, 2010
Caucasian Brazilian
Italy Brazil
2 18
6 39
4 43
12 100
2 14
6 60
7 27
15 101
ff
Ff
FF
Total
ff
Ff
FF
Total
15 1
36 28
47 11
98 40
6 1
32 70
19 14
57 85
tt
Tt
TT
Total
tt
Tt
TT
Total
2
20
18
40
6
44
35
85
AA
Aa
aa
Total
AA
Aa
aa
Total
17
20
3
40
26
51
8
85
Vezzoli, 2002 Mittal, 2010
Caucasian Asian
Italy India
TaqI
Mittal, 2010
Asian
India
ApaI
Mittal, 2010
Asian
India
Association of VDR with urine calcium level
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 01/04/15 For personal use only.
DOI: 10.3109/10799893.2014.936462
3
Figure 1. Association of VDR BsmI gene polymorphism with the urine calcium level in nephrolithiasis patients.
Table 2. Meta analysis of the association of VDR BsmI, Fok1, TaqI with the urine calcium level in nephrolithiasis patients. Genetic contrasts BsmI B versus b BB versus Bb + bb bb versus BB + Bb Fok1 f versus F ff versus Ff + FF FF versus Ff + ff TaqI t versus T tt versus Tt + TT TT versus Tt + tt ApaI A versus a AA versus Aa + aa aa versus AA + Aa
Studies Q test Model number p value selected
OR (95% CI)
p Value
2 2 2
0.31 0.97 0.13
Fixed 0.83(0.57, 1.21) 0.34 Fixed 1.36(0.66, 2.78) 0.40 Fixed 1.75(1.01, 3.02) 0.05
2 2 2
0.98 0.82 0.94
Fixed 0.81(0.57, 1.16) 0.26 Fixed 1.59(0.61, 4.12) 0.34 Fixed 1.87(1.09, 3.22) 0.02
1 1 1
– – –
Fixed 0.87(0.49, 1.55) 0.64 Fixed 0.69(0.13, 3.60) 0.66 Fixed 1.17(0.55, 2.49) 0.69
1 1 1
– – –
Fixed 1.35(0.77, 2.36) 0.29 Fixed 1.68(0.77, 3.65) 0.19 Fixed 0.78(0.20, 3.11) 0.73
Association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients In this meta-analysis, the association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients was not found (A allele: OR ¼ 1.35, 95% CI: 0.77– 2.36, p ¼ 0.29; AA genotype: OR ¼ 1.68, 95% CI: 0.77–3.65, p ¼ 0.19; aa genotype: OR ¼ 0.78, 95% CI: 0.20–3.11, p ¼ 0.73; Figure 4 and Table 2).
Discussion In this meta-analysis for VDR, BsmI bb genotype was associated with the urine calcium level in nephrolithiasis patients, but the B allele and BB genotype was not associated. There were only two included studies for this meta-analysis, and the results might be less robust to some extent. More studies for the association between VDR BsmI gene polymorphism and the urine calcium level in nephrolithiasis patients should be performed in the future. In this meta-analysis, there were two included studies for VDR Fok1 in this meta-analysis, and the results might be slightly robust to some extent. VDR Fok1 FF genotype was associated with the urine calcium level in nephrolithiasis patients, but f allele, and ff genotype not. More studies for the association between VDR Fok1 gene polymorphism and the urine calcium level in nephrolithiasis patients should be performed in the future. In this meta-analysis, VDR TaqI t allele, tt genotype and TT genotype were not associated with the urine calcium level in nephrolithiasis patients. However, there was one included study in this meta-analysis. The results from this metaanalysis should be confirmed in the future. In this meta-analysis, VDR ApaI A allele, AA genotype and aa genotype were not associated with the urine calcium level in nephrolithiasis patients. There was only one recruited study in this meta-analysis. More studies should be conducted in the future.
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Figure 2. Association of VDR Fok1 gene polymorphism with the urine calcium level in nephrolithiasis patients.
Figure 3. Association of VDR TaqI gene polymorphism with the urine calcium level in nephrolithiasis patients.
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DOI: 10.3109/10799893.2014.936462
Association of VDR with urine calcium level
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Figure 4. Association of VDR ApaI gene polymorphism with the urine calcium level in nephrolithiasis patients.
There was no any meta-analysis to study the association of VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the urine calcium level in nephrolithiasis patients using meta-analysis method. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, the number of included studies was small. The conclusion might be less robust, and more studies should be performed in the future. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.
Declaration of interest The authors declare no competing interests. This study was supported by the sub-item of 985 Project Foundation of Sun Yat-Sen (The Hundred Talents Program Foundation; No. 88000-3311300).
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