http://informahealthcare.com/rst ISSN: 1079-9893 (print), 1532-4281 (electronic) J Recept Signal Transduct Res, Early Online: 1–4 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/10799893.2014.926927
RESEARCH ARTICLE
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility Tian-Biao Zhou, Zong-Pei Jiang, and Miao-Fang Huang Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Abstract
Keywords
Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR ¼ 1.12, 95% CI: 0.88–1.44, p ¼ 0.36; BB genotype: OR ¼ 1.15, 95% CI: 0.81–1.62, p ¼ 0.43; bb genotype: OR ¼ 0.86, 95% CI: 0.61–1.20, p ¼ 0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.
Chronic kidney disease, gene polymorphism, meta-analysis, vitamin D receptor
Introduction Endogenous serum metabolite of vitamin D is considered a true steroid hormone, and like glucocorticoids and gonadal hormones, may exert several immunomodulatory activities, and serum vitamin D deficiency, and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, etc (1). Vitamin D receptor (VDR) is a transcription factor that mediates the genomic effects of vitamin D (2). VDR BsmI (rs1544410) gene polymorphism is one of the most important polymorphism types of VDR, and VDR BsmI gene polymorphism have been reported to influence susceptibility to some diseases, such as type 1 diabetes mellitus, (3), type 2 diabetes mellitus (4), rheumatoid arthritis (5), etc. Chronic kidney disease (CKD) is associated with a higher likelihood of progression to end-stage renal disease and increased mortality rates (6). There lacks a well-documented diagnostic approach for the CKD risk, and the etiology of
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]
History Received 28 April 2014 Revised 6 May 2014 Accepted 10 May 2014 Published online 11 June 2014
CKD is not clear. Current evidence indicates that gene polymorphism of some genes are associated with the susceptibility of CKD. Gene polymorphism factor has been reported to be an important factor, which increases the susceptibility of CKD. Most of the epidemiologic investigations studying the relationship between VDR BsmI gene polymorphism and the CKD risk 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. We performed this meta-analysis to investigate whether the VDR BsmI gene polymorphism was associated with the risk of CKD.
Materials and methods Search strategy for the relationship between VDR gene polymorphism and CKD susceptibility The relevant studies were searched from the electronic databases of PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014. The retrieval strategy of ‘‘(vitamin D receptor OR VDR) AND (chronic kidney disease OR CKD)’’ was entered into these databases. The additional reports were identified through references cited in recruited articles.
2
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–4
Inclusion and exclusion criteria
recruited into this meta-analysis (Table 1). The data of our interest were extracted (Table 1).
Inclusion criteria
Association of VDR BsmI gene polymorphism with CKD susceptibility
Inclusion criteria were as follows: (1) The outcome had to be CKD; (2) there had to be at least two comparison groups (case group versus control group); and (3) investigation should provide the data of VDR BsmI genotype distribution.
In this meta-analysis, we found that VDR BsmI B allele, BB genotype and bb genotype were not associated with CKD risk (B allele: OR ¼ 1.12, 95% CI: 0.88–1.44, p ¼ 0.36; BB genotype: OR ¼ 1.15, 95% CI: 0.81–1.62, p ¼ 0.43; bb genotype: OR ¼ 0.86, 95% CI: 0.61–1.20, p ¼ 0.36; Figure 1 for B allele, Figure 2 for BB genotype and Figure 3 for bb genotype; Table 2). In Asian population, B allele, BB genotype and bb genotype were also not associated with the risk of CKD (B allele: OR ¼ 1.16, 95% CI: 0.54–2.49, p ¼ 0.70; BB genotype: OR ¼ 1.54, 95% CI: 0.42–5.61, p ¼ 0.51; bb genotype: OR ¼ 0.85, 95% CI: 0.36–2.03, p ¼ 0.72; Table 2). Furthermore, VDR BsmI gene polymorphism were not associated with CKD risk in Caucasian population (B allele: OR ¼ 1.04, 95% CI: 0.89–1.22, p ¼ 0.61; BB genotype: OR ¼ 1.12, 95% CI: 0.83–1.52, p ¼ 0.46; bb genotype: OR ¼ 0.98, 95% CI: 0.77–1.24, p ¼ 0.85; Table 2).
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
Exclusion criteria Exclusion criteria were as follows: (1) Review articles and editorials; (2) case reports; (3) preliminary result not on VDR BsmI gene polymorphism or outcome; (4) investigating the role VDR BsmI 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 BsmI genotypes. The results were compared and disagreement was resolved by discussion.
Sensitivity analysis In this meta-analysis, the sensitivity analysis was also performed according to HWE test. In our meta-analysis, the gene distribution of VDR BsmI in control group were all in HWE. So, the results for sensitivity analysis were the same as those in non-sensitivity analysis.
Statistical analysis Cochrane Review Manager Version 5 (Cochrane Library, 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 less than 0.1 (7,8). Results were expressed with odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. p50.05 was required for the pooled OR to be statistically significant (9,10). I2 was used to test the heterogeneity among the included studies. A chi-square test using a web-based program was applied to determine if genotype distribution of the control population reported conformed to Hardy–Weinberg equilibrium (HWE; p50.05 was considered significant). Sensitivity analysis was performed if HWE disequilibrium existed.
Discussion VDR BsmI B allele, BB genotype and bb genotype were not associated with CKD risk in overall populations in this metaanalysis. There were nine included studies for this metaanalysis. When the fixed model was taken to calculate the pooled OR for the relationship between VDR BsmI gene polymorphism and CKD risk, the results indicated that VDR BsmI gene polymorphism were associated with CKD risk. However, there was notable heterogeneity among the included studies, and the random effects model was conducted to calculate the pooled OR. The results for overall populations might be improved when more well-designed studies were conducted. Furthermore, in Asian population, B allele, BB genotype and bb genotype were also not associated with the risk of CKD. Furthermore, BsmI B allele, BB genotype and
Results Study characteristics Nine studies (11–19) reporting the relationship between VDR BsmI gene polymorphism and CKD susceptibility were
Table 1. Characteristics of the studies evaluating the effects of VDR BsmI gene polymorphism on CKD risk.
Authors
Ethnicity
Country/ subgroup
Ferna´ndez et al., 1997 Wang and Zhao, 1999 Wu et al., 2004 de Souza et al., 2007 Amato et al., 2008 Testa et al., 2010 Tripathi et al., 2010 El-Shehaby et al., 2013 Santoro et al., 2014
Caucasian Asian Asian Mix Caucasian Caucasian Asian Caucasian Caucasian
Spain China China Brazil Italy Italy India Egypt Italy
Case
Control
Source of control
BB
Bb
bb
Total
BB
Bb
bb
Total
HWE (P)
Population Population Population Population Population Population Population Population Population
27 17 15 27 16 26 12 14 20
58 42 40 63 45 95 99 39 76
49 49 46 23 27 61 147 27 49
134 108 101 113 88 182 258 80 145
16 9 22 15 43 26 4 7 14
67 26 40 22 107 83 131 19 69
37 24 38 22 64 66 434 14 47
120 59 100 59 214 175 569 40 130
0.096 0.657 0.073 0.061 0.887 0.991 0.079 0.899 0.125
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
DOI: 10.3109/10799893.2014.926927
Association of VDR with CKD
Figure 1. Association of VDR BsmI B allele with CKD susceptibility in overall populations.
Figure 2. Association of VDR BsmI BB genotype with CKD susceptibility in overall populations.
Figure 3. Association of VDR BsmI bb genotype with CKD susceptibility in overall populations.
3
4
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–4
Table 2. Meta analysis of the association of VDR BsmI gene polymorphism with CKD risk. Genetic contrasts
Group and subgroups
Studies number
Q test p value
Model selected
B versus b
Overall Asian Caucasian Overall Asian Caucasian Overall Asian Caucasian
9 3 5 9 3 5 9 3 5
0.0001 50.00001 0.97 0.06 0.002 0.68 0.0002 0.0001 0.78
Random Random Fixed Random Random Fixed Random Random Fixed
BB versus Bb+bb
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
bb versus Bb+BB
bb genotype were not associated with CKD risk in Caucasian population. The number of included studies for in Asian population, or in Caucasian population was small, and the results might be less robust. More studies for the association between VDR BsmI gene polymorphism and CKD risk should be performed in the future. In previous study, Mao et al. (20) performed a metaanalysis including six studies to the associations between the BsmI polymorphisms of VDR and end-stage renal disease risk and reported that the B allele, BB genotype and bb genotype of the BsmI polymorphism showed no significant association with end-stage renal disease. The results were similar to ours. In this meta-analysis, we also included some studies performed included the pre-end-stage renal disease data. Our meta-analysis included nine studies and reported that the VDR BsmI B allele BB genotype and bb genotype might not become a valuable indicator to predict the risk of CKD. However, those findings should be regarded cautiously because many other ingredients, such as small sample size of the included report, limited statistical power, heterogeneity of enrolled cases, variable study designs and different interventions, were closely related to affect the results. In conclusion, the VDR BsmI gene polymorphism was not associated with the risk of CKD in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.
6.
7.
8.
9.
10.
11.
12.
13.
14.
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. 880003311300).
15.
16.
References 1. Cutolo M, Paolino S, Sulli A, et al. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci 2014. [Epub ahead of print]. 2. Seuter S, Neme A, Carlberg C. Characterization of genomic Vitamin D receptor binding sites through chromatin looping and opening. PLoS One 2014;9:e96184. 3. 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]. 4. Al-Daghri NM, Al-Attas OS, Alkharfy KM, et al. Association of VDR-gene variants with factors related to the metabolic syndrome, type 2 diabetes and vitamin D deficiency. Gene 2014;542:129–33. 5. Mosaad YM, Hammad EM, Fawzy Z, et al. Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis
17.
18.
19.
20.
OR (95% CI) 1.12 1.16 1.04 1.15 1.54 1.12 0.86 0.85 0.98
(0.88–1.44) (0.54–2.49) (0.89–1.22) (0.81–1.62) (0.42–5.61) (0.83–1.52) (0.61–1.20) (0.36–2.03) (0.77–1.24)
p 0.36 0.70 0.61 0.43 0.51 0.46 0.36 0.72 0.85
and rheumatoid related osteoporosis. Hum Immunol 2014;75: 452–61. Demirjian S, Lane BR, Derweesh IH, et al. Chronic kidney disease due to surgical removal of nephrons: relative rates of progression and survival. J Urol 2014. [Epub ahead of print]. Zhou TB, Drummen GP, Jiang ZP, et al. Association of peroxisome proliferator-activated receptors/retinoic acid receptors with renal diseases. J Recept Signal Transduct Res 2013;33:349–52. Zhou TB, Qin YH, Su LN, et al. The association between angiotensin-converting enzyme insertion/deletion gene variant and risk of focal segmental glomerulosclerosis: a systematic review and meta-analysis. J Renin Angiotensin Aldosterone Syst 2011;12: 624–33. Zhou TB, Qin YH, Su LN, et al. ACE I/D gene polymorphism can’t predict the steroid responsiveness in Asian children with idiopathic nephrotic syndrome: a meta-analysis. PLoS One 2011;6:e19599. 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. Fernandez E, Fibla J, Betriu A, et al. Association between vitamin D receptor gene polymorphism and relative hypoparathyroidism in patients with chronic renal failure. J Am Soc Nephrol 1997;8: 1546–52. Wang X, Zhao W. Association between vitamin D receptor gene polymorphism and secondary hyperparathyrodism in Chinese with chronic renal failure. J Nephrol Dialy Transplant 1999;8: 124–202. Wu H, Bao Y, Xie R. Relationship between vitamin D receptor gene polymorphism and secondary hyperparathyroidism in patients with chronic renal failure. J Harbin Med Univ 2004;38:269–71. de Souza CM, Braosi AP, Luczyszyn SM, et al. Association between vitamin D receptor gene polymorphisms and susceptibility to chronic kidney disease and periodontitis. Blood Purif 2007;25: 411–9. Amato M, Pacini S, Aterini S, et al. Iron indices and vitamin D receptor polymorphisms in hemodialysis patients. Adv Chronic Kidney Dis 2008;15:186–90. Testa A, Mallamaci F, Benedetto FA, et al. Vitamin D receptor (VDR) gene polymorphism is associated with left ventricular (LV) mass and predicts left ventricular hypertrophy (LVH) progression in end-stage renal disease (ESRD) patients. J Bone Miner Res 2010; 25:313–9. Tripathi G, Sharma R, Sharma RK, et al. Vitamin D receptor genetic variants among patients with end-stage renal disease. Ren Fail 2010;32:969–77. El-Shehaby AM, El-Khatib MM, Marzouk S, et al. Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients. Scand J Clin Lab Invest 2013;73:75–81. 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. Mao S, Huang S. Lack of an association between vitamin D receptor BsmI gene polymorphism and the risk of end-stage renal disease: a meta-analysis. Intern Med 2013;52:2423–30.
RESEARCH ARTICLE
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility Tian-Biao Zhou, Zong-Pei Jiang, and Miao-Fang Huang Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Abstract
Keywords
Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR ¼ 1.12, 95% CI: 0.88–1.44, p ¼ 0.36; BB genotype: OR ¼ 1.15, 95% CI: 0.81–1.62, p ¼ 0.43; bb genotype: OR ¼ 0.86, 95% CI: 0.61–1.20, p ¼ 0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.
Chronic kidney disease, gene polymorphism, meta-analysis, vitamin D receptor
Introduction Endogenous serum metabolite of vitamin D is considered a true steroid hormone, and like glucocorticoids and gonadal hormones, may exert several immunomodulatory activities, and serum vitamin D deficiency, and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, etc (1). Vitamin D receptor (VDR) is a transcription factor that mediates the genomic effects of vitamin D (2). VDR BsmI (rs1544410) gene polymorphism is one of the most important polymorphism types of VDR, and VDR BsmI gene polymorphism have been reported to influence susceptibility to some diseases, such as type 1 diabetes mellitus, (3), type 2 diabetes mellitus (4), rheumatoid arthritis (5), etc. Chronic kidney disease (CKD) is associated with a higher likelihood of progression to end-stage renal disease and increased mortality rates (6). There lacks a well-documented diagnostic approach for the CKD risk, and the etiology of
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]
History Received 28 April 2014 Revised 6 May 2014 Accepted 10 May 2014 Published online 11 June 2014
CKD is not clear. Current evidence indicates that gene polymorphism of some genes are associated with the susceptibility of CKD. Gene polymorphism factor has been reported to be an important factor, which increases the susceptibility of CKD. Most of the epidemiologic investigations studying the relationship between VDR BsmI gene polymorphism and the CKD risk 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. We performed this meta-analysis to investigate whether the VDR BsmI gene polymorphism was associated with the risk of CKD.
Materials and methods Search strategy for the relationship between VDR gene polymorphism and CKD susceptibility The relevant studies were searched from the electronic databases of PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014. The retrieval strategy of ‘‘(vitamin D receptor OR VDR) AND (chronic kidney disease OR CKD)’’ was entered into these databases. The additional reports were identified through references cited in recruited articles.
2
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–4
Inclusion and exclusion criteria
recruited into this meta-analysis (Table 1). The data of our interest were extracted (Table 1).
Inclusion criteria
Association of VDR BsmI gene polymorphism with CKD susceptibility
Inclusion criteria were as follows: (1) The outcome had to be CKD; (2) there had to be at least two comparison groups (case group versus control group); and (3) investigation should provide the data of VDR BsmI genotype distribution.
In this meta-analysis, we found that VDR BsmI B allele, BB genotype and bb genotype were not associated with CKD risk (B allele: OR ¼ 1.12, 95% CI: 0.88–1.44, p ¼ 0.36; BB genotype: OR ¼ 1.15, 95% CI: 0.81–1.62, p ¼ 0.43; bb genotype: OR ¼ 0.86, 95% CI: 0.61–1.20, p ¼ 0.36; Figure 1 for B allele, Figure 2 for BB genotype and Figure 3 for bb genotype; Table 2). In Asian population, B allele, BB genotype and bb genotype were also not associated with the risk of CKD (B allele: OR ¼ 1.16, 95% CI: 0.54–2.49, p ¼ 0.70; BB genotype: OR ¼ 1.54, 95% CI: 0.42–5.61, p ¼ 0.51; bb genotype: OR ¼ 0.85, 95% CI: 0.36–2.03, p ¼ 0.72; Table 2). Furthermore, VDR BsmI gene polymorphism were not associated with CKD risk in Caucasian population (B allele: OR ¼ 1.04, 95% CI: 0.89–1.22, p ¼ 0.61; BB genotype: OR ¼ 1.12, 95% CI: 0.83–1.52, p ¼ 0.46; bb genotype: OR ¼ 0.98, 95% CI: 0.77–1.24, p ¼ 0.85; Table 2).
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
Exclusion criteria Exclusion criteria were as follows: (1) Review articles and editorials; (2) case reports; (3) preliminary result not on VDR BsmI gene polymorphism or outcome; (4) investigating the role VDR BsmI 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 BsmI genotypes. The results were compared and disagreement was resolved by discussion.
Sensitivity analysis In this meta-analysis, the sensitivity analysis was also performed according to HWE test. In our meta-analysis, the gene distribution of VDR BsmI in control group were all in HWE. So, the results for sensitivity analysis were the same as those in non-sensitivity analysis.
Statistical analysis Cochrane Review Manager Version 5 (Cochrane Library, 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 less than 0.1 (7,8). Results were expressed with odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. p50.05 was required for the pooled OR to be statistically significant (9,10). I2 was used to test the heterogeneity among the included studies. A chi-square test using a web-based program was applied to determine if genotype distribution of the control population reported conformed to Hardy–Weinberg equilibrium (HWE; p50.05 was considered significant). Sensitivity analysis was performed if HWE disequilibrium existed.
Discussion VDR BsmI B allele, BB genotype and bb genotype were not associated with CKD risk in overall populations in this metaanalysis. There were nine included studies for this metaanalysis. When the fixed model was taken to calculate the pooled OR for the relationship between VDR BsmI gene polymorphism and CKD risk, the results indicated that VDR BsmI gene polymorphism were associated with CKD risk. However, there was notable heterogeneity among the included studies, and the random effects model was conducted to calculate the pooled OR. The results for overall populations might be improved when more well-designed studies were conducted. Furthermore, in Asian population, B allele, BB genotype and bb genotype were also not associated with the risk of CKD. Furthermore, BsmI B allele, BB genotype and
Results Study characteristics Nine studies (11–19) reporting the relationship between VDR BsmI gene polymorphism and CKD susceptibility were
Table 1. Characteristics of the studies evaluating the effects of VDR BsmI gene polymorphism on CKD risk.
Authors
Ethnicity
Country/ subgroup
Ferna´ndez et al., 1997 Wang and Zhao, 1999 Wu et al., 2004 de Souza et al., 2007 Amato et al., 2008 Testa et al., 2010 Tripathi et al., 2010 El-Shehaby et al., 2013 Santoro et al., 2014
Caucasian Asian Asian Mix Caucasian Caucasian Asian Caucasian Caucasian
Spain China China Brazil Italy Italy India Egypt Italy
Case
Control
Source of control
BB
Bb
bb
Total
BB
Bb
bb
Total
HWE (P)
Population Population Population Population Population Population Population Population Population
27 17 15 27 16 26 12 14 20
58 42 40 63 45 95 99 39 76
49 49 46 23 27 61 147 27 49
134 108 101 113 88 182 258 80 145
16 9 22 15 43 26 4 7 14
67 26 40 22 107 83 131 19 69
37 24 38 22 64 66 434 14 47
120 59 100 59 214 175 569 40 130
0.096 0.657 0.073 0.061 0.887 0.991 0.079 0.899 0.125
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
DOI: 10.3109/10799893.2014.926927
Association of VDR with CKD
Figure 1. Association of VDR BsmI B allele with CKD susceptibility in overall populations.
Figure 2. Association of VDR BsmI BB genotype with CKD susceptibility in overall populations.
Figure 3. Association of VDR BsmI bb genotype with CKD susceptibility in overall populations.
3
4
T.-B. Zhou et al.
J Recept Signal Transduct Res, Early Online: 1–4
Table 2. Meta analysis of the association of VDR BsmI gene polymorphism with CKD risk. Genetic contrasts
Group and subgroups
Studies number
Q test p value
Model selected
B versus b
Overall Asian Caucasian Overall Asian Caucasian Overall Asian Caucasian
9 3 5 9 3 5 9 3 5
0.0001 50.00001 0.97 0.06 0.002 0.68 0.0002 0.0001 0.78
Random Random Fixed Random Random Fixed Random Random Fixed
BB versus Bb+bb
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by Selcuk Universitesi on 12/22/14 For personal use only.
bb versus Bb+BB
bb genotype were not associated with CKD risk in Caucasian population. The number of included studies for in Asian population, or in Caucasian population was small, and the results might be less robust. More studies for the association between VDR BsmI gene polymorphism and CKD risk should be performed in the future. In previous study, Mao et al. (20) performed a metaanalysis including six studies to the associations between the BsmI polymorphisms of VDR and end-stage renal disease risk and reported that the B allele, BB genotype and bb genotype of the BsmI polymorphism showed no significant association with end-stage renal disease. The results were similar to ours. In this meta-analysis, we also included some studies performed included the pre-end-stage renal disease data. Our meta-analysis included nine studies and reported that the VDR BsmI B allele BB genotype and bb genotype might not become a valuable indicator to predict the risk of CKD. However, those findings should be regarded cautiously because many other ingredients, such as small sample size of the included report, limited statistical power, heterogeneity of enrolled cases, variable study designs and different interventions, were closely related to affect the results. In conclusion, the VDR BsmI gene polymorphism was not associated with the risk of CKD in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.
6.
7.
8.
9.
10.
11.
12.
13.
14.
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. 880003311300).
15.
16.
References 1. Cutolo M, Paolino S, Sulli A, et al. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci 2014. [Epub ahead of print]. 2. Seuter S, Neme A, Carlberg C. Characterization of genomic Vitamin D receptor binding sites through chromatin looping and opening. PLoS One 2014;9:e96184. 3. 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]. 4. Al-Daghri NM, Al-Attas OS, Alkharfy KM, et al. Association of VDR-gene variants with factors related to the metabolic syndrome, type 2 diabetes and vitamin D deficiency. Gene 2014;542:129–33. 5. Mosaad YM, Hammad EM, Fawzy Z, et al. Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis
17.
18.
19.
20.
OR (95% CI) 1.12 1.16 1.04 1.15 1.54 1.12 0.86 0.85 0.98
(0.88–1.44) (0.54–2.49) (0.89–1.22) (0.81–1.62) (0.42–5.61) (0.83–1.52) (0.61–1.20) (0.36–2.03) (0.77–1.24)
p 0.36 0.70 0.61 0.43 0.51 0.46 0.36 0.72 0.85
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