Evaluating the Association between TaqI Variant of Vitamin D Receptor Gene and Susceptibility to Tuberculosis: A Meta"‘analysis



Meta"‘analysis, tuberculosis, vitamin D receptor


Objectives: Vitamin D has been shown to hamper the growth of Mycobacterium tuberculosis in macrophages. The actions of vitamin D are exerted through a vitamin D receptor (VDR). The genetic variant TaqI of VDR has been implicated in tuberculosis (TB) risk in several case"‘control studies. However, these studies have shown inconsistent results. Hence, a meta"‘analysis was conducted to investigate the potential relationship between VDR TaqI polymorphism and risk of developing TB. Materials and Methods: We performed a quantitative synthesis for published studies based upon the relationship between TaqI polymorphism and TB risk from PubMed (Medline) and Embase databases. The meta"‘analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for all genetic models. Results: A total of 21 studies including 2,960 TB cases and 3,894 controls were included in this study. The pooled analysis demonstrated no evidence of association between VDR TaqI genotypes and risk of TB in any of the genetic models; variant (t vs T: P = 0.618; OR = 1.051, 95% CI = 0.864–1.278), homozygous (tt vs TT: P = 0.120; OR = 1.336, 95% CI = 0.927–1.924), heterozygous (Tt vs TT: P = 0.925; OR = 0.988, 95% CI = 0.774–1.262), dominant model (tt + Tt vs TT: P = 0.805; OR = 1.032, 95% CI = 0.805–1.322), and recessive model (tt vs TT + Tt: P = 0.180; OR = 1.229, 95% CI = 0.909–1.660). No publication bias was detected during the analysis. Conclusions: Overall findings of this meta"‘analysis suggest that genetic polymorphism TaqI of VDR gene may not contribute to the risk of TB. However, future larger studies with group of populations are warranted to analyze this relationship.


Download data is not yet available.


Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990 − 2020: Global Burden of Disease Study.Lancet 1997;349:1498"‘504.

Rosman MD, Oner"‘Eyupoglu AF. Clinical presentation and treatment of tuberculosis. In: Fishman AP, editor. Fishman's Pulmonary Diseases and Disorders. New York: McGraw"‘Hill; 1998. p. 2483"‘502.

Nava"‘Aguilera E, Andersson N, Harris E, Mitchell S, Hamel C, Shea B, et al. Risk factors associated with recent transmission of tuberculosis: Systematic review and meta"‘analysis. Int J Tuberc Lung Dis 2009;13:17"‘26.

Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325"‘49.

Deluca HF, Cantorna MT. Vitamin D: Its role and uses in immunology. FASEB J 2001;15:2579"‘85.

Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 2000;22:203"‘17.

Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284"‘7.

Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, et al. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 2001;177:145"‘59.

Bellamy R. Evidence of gene"‘environment interaction in development of tuberculosis. Lancet 2000;355:588"‘9.

Wu F, Zhang W, Zhang L, Wu J, Li C, Meng X, et al. NRAMP1, VDR, HLA"‘DRB1, and HLA"‘DQB1 gene polymorphisms in susceptibility to tuberculosis among the Chinese Kazakh population: A case"‘control study. Biomed Res Int 2013;2013:484535.

Singh A, Gaughan JP, Kashyap VK. SLC11A1 and VDR gene variants and susceptibility to tuberculosis and disease progression in East India. Int J Tuberc Lung Dis 2011;15:1468"‘74.

Kang TJ, Jin SH, Yeum CE, Lee SB, Kim CH, Lee SH, et al. Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis. Immune Netw 2011;11:253"‘7.

Sharma PR, Singh S, Jena M, Mishra G, Prakash R, Das PK, et al. Coding and non"‘coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India. Infect Genet Evol 2011;11:1456"‘61.

Ates O, Dolek B, Dalyan L, Musellim B, Ongen G, Topal"‘Sarikaya A. The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis. Mol Biol Rep 2011;38:2633"‘6.

Banoei MM, Mirsaeidi MS, Houshmand M, Tabarsi P, Ebrahimi G, Zargari L, et al. Vitamin D receptor homozygote mutant tt and bb are associated with susceptibility to pulmonary tuberculosis in the Iranian population. Int J Infect Dis 2010;14:e84"‘5.

Alagarasu K, Selvaraj P, Swaminathan S, Narendran G, Narayanan PR. 5' regulatory and 3' untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV"‘TB patients. J Clin Immunol 2009;29:196"‘204.

Selvaraj P, Prabhu Anand S, Harishankar M, Alagarasu K. Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin D receptor and cathelicidin in pulmonary tuberculosis. J Clin Immunol 2009;29:470"‘8.

Vidyarani M, Selvaraj P, Raghavan S, Narayanan PR. Regulatory role of 1,25"‘dihydroxy vitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis. Exp Mol Pathol 2009;86:69"‘73.

Selvaraj P, Vidyarani M, Alagarasu K, Prabhu Anand S, Narayanan PR. Regulatory role of promoter and 3' UTR variants of vitamin D receptor gene on cytokine response in pulmonary tuberculosis. J Clin Immunol 2008;28:306"‘13.

Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P,et al. DC"‘SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun 2007;8:456"‘67.

Babb C, van der Merwe L, Beyers N, Pheiffer C, Walzl G, Duncan K, et al. Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary tuberculosis patients. Tuberculosis (Edinb) 2007;87:295"‘302.

Lombard Z, Dalton DL, Venter PA, Williams RC, Bornman L. Association of HLA"‘DR, "‘DQ, and vitamin D receptor alleles and haplotypes with tuberculosis in the Venda of South Africa. Hum Immunol 2006;67:643"‘54.

Liu W, Cao WC, Zhang CY, Tian L, Wu XM, Habbema JD, et al. VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: A case"‘control study. Int J Tuberc Lung Dis 2004;8:428"‘34.

Bornman L, Campbell SJ, Fielding K, Bah B, Sillah J, Gustafson P, et al. Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: A case"‘control and family study. J Infect Dis 2004;190:1631"‘41.

Roth DE, Soto G, Arenas F, Bautista CT, Ortiz J, Rodriguez R, et al. Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis. J Infect Dis 2004;190:920"‘7.

Selvaraj P, Chandra G, Jawahar MS, Rani MV, Rajeshwari DN, Narayanan PR. Regulatory role of vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on macrophage phagocytosis and lymphoproliferative response to Mycobacterium tuberculosis antigen in pulmonary tuberculosis. J Clin Immunol 2004;24:523"‘32.

Selvaraj P, Kurian SM, Chandra G, Reetha AM, Charles N, Narayanan PR. Vitamin D receptor gene variants of BsmI, ApaI, TaqI, and FokI polymorphisms in spinal tuberculosis. Clin Genet 2004;65:73"‘6.

Delgado JC, Baena A, Thim S, Goldfeld AE. Ethnic"‘specific genetic associations with pulmonary tuberculosis. J Infect Dis 2002;186:1463"‘8.

Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: A case"‘control study. Lancet 2000;355:618"‘21.

Bellamy R, Ruwende C, Corrah T, McAdam KP, Thursz M, Whittle HC, et al. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 1999;179:721"‘4.

Cohn LD, Becker BJ. How meta"‘analysis increases statistical power. Psychol Methods 2003;8:243"‘53.

Areeshi MY, Mandal RK, Panda AK, Bisht SC, Haque S. CD14 "‘159 C>T gene polymorphism with increased risk of tuberculosis: Evidence from a meta"‘analysis. PLoS One 2013;8:e64747.

Wu R, Li B. A multiplicative"‘epistatic model for analyzing interspecific differences in outcrossing species. Biometrics 1999;55:355"‘65.

Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719"‘48.

DerSimonian R, Laird N. Meta"‘analysis in clinical trials. Control Clin Trials 1986;7:177"‘88.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta"‘analyses. BMJ 2003;327:557"‘60.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta"‘analysis detected by a simple, graphical test. BMJ 1997;315:629"‘34.

Rostand SG, Warnock DG. Introduction to vitamin D symposium, March 14, 2008. Clin J Am Soc Nephrol 2008;3:1534.

Rockett KA, Brookes R, Udalova I, Vidal V, Hill AV, Kwiatkowski D. 1,25"‘Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage"‘like cell line. Infect Immun 1998;66:5314"‘21.

Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev 2008;29:726"‘76.

Hill AV. The genomics and genetics of human infectious disease susceptibility. Annu Rev Genomics Hum Genet 2001;2:373"‘400.

Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR, et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub"‘Saharan Africa. Clin Infect Dis 2008;46:443"‘6.

Sita"‘Lumsden A, Lapthorn G, Swaminathan R, Milburn HJ. Reactivation of tuberculosis and vitamin D deficiency: The contribution of diet and exposure to sunlight. Thoraí—2007;62:1003"‘7.

Ioannidis JP, Boffetta P, Little J, O'Brien TR, Uitterlinden AG, Vineis P, et al. Assessment of cumulative evidence on genetic associations: Interim guidelines. Int J Epidemiol 2008;37:120"‘32.

Gao L, Tao Y, Zhang L, Jin Q. Vitamin D receptor genetic polymorphisms and tuberculosis: Updated systematic review and meta"‘analysis. Int J Tuberc Lung Dis 2010;14:15"‘23.

Lewis SJ, Baker I, Davey Smith G. Meta"‘analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk. Int J Tuberc Lung Dis 2005;9:1174"‘7.

Cao S, Luo PF, Li W, Tang WQ, Cong XN, Wei PM. Vitamin D receptor genetic polymorphisms and tuberculosis among Chinese Han ethnic group. Chin Med J (Engl) 2012;125:920"‘5.

Bellamy R. Genome"‘wide approaches to identifying genetic factors in host susceptibility to tuberculosis. Microbes Infect 2006;8:1119"‘23.

Möller M, Hoal EG. Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis (Edinb) 2010;90:71"‘83.

Bamshad M, Wooding SP. Signatures of natural selection in the human genome. Nat Rev Genet 2003;4:99"‘111.

Chen C, Liu Q, Zhu L, Yang H, Lu W. Vitamin Dreceptor gene polymorphisms on the risk of tuberculosis, a meta"‘analysis of 29 case"‘control studies. Plos One 8 (12): e83843. doi: 10.1371/journal.pone. 0083843.



How to Cite

Areeshi, M. Y., Mandal, R. K., Akhter, N., Panda, A. K., & Haque, S. (2018). Evaluating the Association between TaqI Variant of Vitamin D Receptor Gene and Susceptibility to Tuberculosis: A Meta"‘analysis. Toxicology International, 21(2), 140–147. Retrieved from https://www.informaticsjournals.com/index.php/toxi/article/view/20993



Original Research