Skip to main content
SpringerLink
Log in

Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies

  • Review article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Background

Evidence from various studies suggest that vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes (T2D); However, these results have been disputable. Here we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms and susceptibility to T2D.

Methods

All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T2D published up to August 2020 were identified by comprehensive systematic database search in web of science, Scopus, and Medline. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure strength of association. The methodological quality of each study was assessed according to the Newcastle–Ottawa Scale. Subgroup and meta-regression analysis were also performed.

Results

A total of 47 case–control studies were included in this meta-analysis. The overall population results revealed a significant association between FokI, and BsmI (heterozygote model) polymorphisms and T2D in the overall analysis. However, no association was found with the TaqI and ApaI polymorphisms. Moreover, the pooled results of subgroup analysis by ethnicity suggested significant association between FokI, TaqI, and BsmI polymorphisms and T2D in some subgroups. Meta-regression analyses indicated that none of the publication year, ethnicity, and genotyping method were the source of heterogenicity in all four polymorphisms.

Conclusions

This meta-analysis suggested a significant association between VDR gene FokI, and BsmI (heterozygote model) polymorphisms and T2D susceptibility in overall population and ethnic-specific analysis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

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

Abbreviations

T2DM:

Type 2 diabetes mellitus

VDR:

Vitamin D receptor

VitD:

Vitamin D,

SNP:

Single nucleotide polymorphisms

IL:

Interleukin

PRISMA:

Preferred Reporting Items for Systematic reviews and Meta-Analyses

NOS:

Newcastle-Ottawa Scale

UVR:

Ultraviolet radiation

Th:

T helper

TNF:

Tumor necrosis factor

IFN:

Interferon; HWE, Hardy–Weinberg equilibrium

PCR- RFLP:

Polymerase chain reaction-restriction fragment length polymorphism.

References

  1. Ozougwu J, et al. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. J Physiol Pathophysiol. 2013;4(4):46–57.

    Article  Google Scholar 

  2. Federation., I.D., IDF Diabetes Atlas, 8th ed. International Diabetes Federation: Brussels,Belgium, 2017.

  3. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.

    Article  CAS  PubMed  Google Scholar 

  4. Cho N, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.

    Article  CAS  Google Scholar 

  5. Kautzky-Willer A, Harreiter J, Pacini G. Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocr Rev. 2016;37(3):278–316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2016;92(1084):63–9.

    Article  CAS  PubMed  Google Scholar 

  7. Ofstad AP, Atar D, Gullestad L, Langslet G, Johansen OE. The heart failure burden of type 2 diabetes mellitus—a review of pathophysiology and interventions. Heart Fail Rev. 2018;23(3):303–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Todd JN, Srinivasan S, Pollin TI. Advances in the genetics of youth-onset type 2 diabetes. Current diabetes reports. 2018;18(8):57.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sergeev IN, Rhoten WB. 1, 25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology. 1995;136(7):2852–61.

    Article  CAS  PubMed  Google Scholar 

  11. Maestro B, Molero S, Bajo S, Dávila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1, 25-dihydroxyvitamin D3. Cell Biochemistry and Function: Cellular biochemistry and its modulation by active agents or disease. 2002;20(3):227–32.

    Article  CAS  Google Scholar 

  12. Dunlop TW, Väisänen S, Frank C, Molnár F, Sinkkonen L, Carlberg C. The human peroxisome proliferator-activated receptor δ gene is a primary target of 1α, 25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol. 2005;349(2):248–60.

    Article  CAS  PubMed  Google Scholar 

  13. Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function: a novel role for extra-renal 1α-hydroxylase. Mol Cell Endocrinol. 2004;215(1–2):31–8.

    Article  CAS  PubMed  Google Scholar 

  14. Uitterlinden AG, Fang Y, van Meurs JBJ, Pols HAP, van Leeuwen JPTM. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143–56.

    Article  CAS  PubMed  Google Scholar 

  15. Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia. 2005;48(7):1247–57.

    Article  CAS  PubMed  Google Scholar 

  16. Imani, D., et al., Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. 2019. 19(1): p. 339.

  17. Makoui, M.H., et al., Vitamin D receptor gene polymorphism and susceptibility to asthma: meta-analysis based on 17 case-control studies. 2020. 124(1): p. 57–69.

  18. Reis, G.V.O.P.d., et al., Vitamin D receptor polymorphisms and the polycystic ovary syndrome: A systematic review. Journal of Obstetrics and Gynaecology Research, 2017. 43(3): p. 436–446.

  19. Xavier LB, Gontijo NA, Rodrigues KF, Cândido AL, dos Reis FM, de Sousa MCR, et al. Polymorphisms in vitamin D receptor gene, but not vitamin D levels, are associated with polycystic ovary syndrome in Brazilian women. Gynecol Endocrinol. 2019;35(2):146–9.

    Article  CAS  PubMed  Google Scholar 

  20. Sakharkar, P., Vitamin D receptor (VDR) gene polymorphism: implications on non-bone diseases. Journal of Basic and Clinical Pharmacy, 2017.

    Google Scholar 

  21. Zhai, N., et al., Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis. 2020.

    Google Scholar 

  22. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.

    Article  PubMed  Google Scholar 

  23. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.

    Article  PubMed  Google Scholar 

  24. Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods. 2006;11(2):193–206.

    Article  PubMed  Google Scholar 

  25. DerSimonian, R. and N. Laird, Meta-analysis in clinical trials control Clin trials 7: 177–188. Find this article online, 1986.

    Google Scholar 

  26. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.

    CAS  PubMed  Google Scholar 

  27. Begg, C.B. and M. Mazumdar, Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994: p. 1088–1101, Operating Characteristics of a Rank Correlation Test for Publication Bias, 50.

  28. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629–34.

    Article  CAS  PubMed  Google Scholar 

  29. Malecki M, et al. Vitamin D receptor gene polymorphisms and association with type 2 diabetes mellitus in a polish population. Exp Clin Endocrinol Diabetes. 2003;111(08):505–9.

    Article  CAS  PubMed  Google Scholar 

  30. Vedralová M, Kotrbova-Kozak A, Zelezníková V, Zoubková H, Rychlík I, Cerná M. Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications, diabetic nephropathy and non-diabetic renal disease. Kidney Blood Press Res. 2012;36(1):1–9.

    Article  PubMed  Google Scholar 

  31. Bertoccini L, Sentinelli F, Leonetti F, Bailetti D, Capoccia D, Cimini FA, et al. The vitamin D receptor functional variant rs2228570 (C> T) does not associate with type 2 diabetes mellitus. Endocr Res. 2017;42(4):331–5.

    Article  CAS  PubMed  Google Scholar 

  32. Al Safar H, et al. Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus. J Steroid Biochem Mol Biol. 2018;175:119–24.

    Article  PubMed  Google Scholar 

  33. Sarma D, Chauhan VS, Saikia KK, Sarma P, Nath S. Prevalence pattern of key polymorphisms in the vitamin D receptor gene among patients of type 2 diabetes mellitus in Northeast India. Indian journal of endocrinology and metabolism. 2018;22(2):229–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gnanaprakash V, et al. Association of Vitamin D receptor (TaqI, BsmI, and FokI) polymorphisms with prediabetes and type 2 diabetes in Asian Indians. Journal of Diabetology. 2019;10(1):29.

    Article  Google Scholar 

  35. Xia Z, Hu Y, Han Z, Gao Y, Bai J, He Y, et al. Association of vitamin D receptor gene polymorphisms with diabetic dyslipidemia in the elderly male population in North China. Clin Interv Aging. 2017;12:1673–9.

    Article  CAS  PubMed  Google Scholar 

  36. TANEJA N, KHADAGAWAT R, MANI S. Vitamin d receptor gene polymorphisms and haplotype analysis in type 2 diabetes mellitus patients from North India. Asian J Pharm Clin Res. 2017;10(10):248–52.

    Article  CAS  Google Scholar 

  37. Wang X, et al. Vitamin D receptor gene FokI but not TaqI, ApaI, BsmI polymorphism is associated with Hashimoto’s thyroiditis: a meta-analysis. Scientific reports. 2017;7:41540.

    Article  CAS  PubMed  Google Scholar 

  38. Soroush N, Radfar M, Hamidi AK, Abdollahi M, Qorbani M, Razi F, et al. Vitamin D receptor gene FokI variant in diabetic foot ulcer and its relation with oxidative stress. Gene. 2017;599:87–91.

    Article  CAS  PubMed  Google Scholar 

  39. Zhong X, du Y, Lei Y, Liu N, Guo Y, Pan T. Effects of vitamin D receptor gene polymorphism and clinical characteristics on risk of diabetic retinopathy in Han Chinese type 2 diabetes patients. Gene. 2015;566(2):212–6.

    Article  CAS  PubMed  Google Scholar 

  40. Shab-Bidar S, Neyestani TR, Djazayery A. Vitamin D receptor gene polymorphisms, metabolic syndrome, and type 2 diabetes in Iranian subjects: no association with observed SNPs. Int J Vitam Nutr Res. 2017;10:1–10.

    Google Scholar 

  41. Jia J, Ding H, Yang K, Mao L, Zhao H, Zhan Y, et al. Vitamin D receptor genetic polymorphism is significantly associated with risk of type 2 diabetes mellitus in Chinese Han population. Arch Med Res. 2015;46(7):572–9.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang H, Wang J, Yi B, Zhao Y, Liu Y, Zhang K, et al. 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  PubMed  Google Scholar 

  43. Hadi SM, Al-Zubaidy R. Genotyping of vitamin D receptor FOKI polymorphism as a predictor for type 2 diabetes mellitus by a tetra primer-ARMS-PCR assay. Gene Reports. 2019;15:100362.

    Article  Google Scholar 

  44. Al-Daghri NM, et al. Vitamin D receptor gene polymorphisms and HLA DRB1* 04 cosegregation in Saudi type 2 diabetes patients. J Immunol. 2012;188(3):1325–32.

    Article  CAS  PubMed  Google Scholar 

  45. Dong X, et al. Study on the association between vitamin D receptor gene fokI (T/C) polymorphisms and the susceptibility to type 2 diabetic kidney disease of Han nationality in south of China. International Journal of Molecular Epidemiology and Genetics. 2018;9(5):55.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Bid, H.K., et al., Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study. Indian J Med Sci, 2009. 63(5).

  47. Ma L, et al. Diminished 25-OH vitamin D3 levels and vitamin D receptor variants are associated with susceptibility to type 2 diabetes with coronary artery diseases. J Clin Lab Anal. 2020;34(4):e23137.

    Article  CAS  PubMed  Google Scholar 

  48. Sattar, N.A. and F. Hussain, Vitamin D receptor FokI polymorphism in a Pakistani population with type 2 diabetes mellitus. Pak J Pharm Sci, 2020. 33(2).

  49. El Gendy HI, et al. Vitamin D receptor gene polymorphisms and 25 (OH) vitamin D: lack of association to glycemic control and metabolic parameters in type 2 diabetic Egyptian patients. Journal of clinical & translational endocrinology. 2019;15:25–9.

    Article  Google Scholar 

  50. Rasheed MA, Kantoush N, Abd el-Ghaffar N, Farouk H, Kamel S, Ibrahim AA, et al. Expression of JAZF1, ABCC8, KCNJ11and Notch2 genes and vitamin D receptor polymorphisms in type 2 diabetes, and their association with microvascular complications. Therapeutic advances in endocrinology and metabolism. 2017;8(6):97–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mahjoubi I, Kallel A, Sbaï MH, Ftouhi B, Ben Halima M, Jemaa Z, et al. Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population. Indian J Med Res. 2016;144(1):46–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mackawy AM, Badawi ME. Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients. Meta gene. 2014;2:540–56.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Skorpen CG, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75(5):795–810.

    Article  CAS  Google Scholar 

  54. Maia J, Silva A, Carmo R, Mendonça T, Griz L, Moura P, et al. The association between vitamin D receptor gene polymorphisms (TaqI and FokI), type 2 diabetes, and micro−/macrovascular complications in postmenopausal women. Appl Clin Genet. 2016;9:131–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Angel B, Lera L, Márquez C, Albala C. The association of VDR polymorphisms and type 2 diabetes in older people living in community in Santiago de Chile. Nutrition & diabetes. 2018;8(1):31.

    Article  Google Scholar 

  56. Rodrigues KF, Pietrani NT, Bosco AA, de Sousa MCR, Silva IFO, Silveira JN, et al. Lower vitamin D levels, but not VDR polymorphisms, influence type 2 diabetes mellitus in Brazilian population independently of obesity. Medicina. 2019;55(5):188.

    Article  PubMed Central  Google Scholar 

  57. Pinho RC, et al. Polymorphisms of the vitamin D receptor gene (FOKI, CDX 2, and GATA) and susceptibility to chronic periodontitis in diabetic and non-diabetic individuals: a case-control study. J Investig Clin Dent. 2019;10(1):e12370.

    Article  PubMed  Google Scholar 

  58. Mukhopadhyaya P, et al. Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population. Genet Mol Res. 2010;9(4):2060–8.

    Article  CAS  PubMed  Google Scholar 

  59. Boullu-Sanchis S, Leprêtre F, Hedelin G, Donnet JP, Schaffer P, Froguel P, et al. Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism. Diabetes and Metabolism. 1999;25(2):150–6.

    CAS  PubMed  Google Scholar 

  60. AL-Darraji, S.Z., H.F. AL-Azzawie, and A.M. AL-Kharsani, Associations between TaqI Polymorphisms in Vitamin D Receptor Gene and Type 2 Diabetes Mellitus in Obese Iraqi Population. JOURNAL OF DIABETES & METABOLISM, 2017. 8(4).

  61. Malik R, Farooq R, Mehta P, Ishaq S, Din I, Shah P, et al. Association of Vitamin D Receptor Gene Polymorphism in adults with type 2 diabetes in the Kashmir Valley. Can J Diabetes. 2018;42(3):251–6.

    Article  PubMed  Google Scholar 

  62. Saxena M, et al. Eleven genetic variants of seven important candidate genes involved in manifestation of type 2 diabetes mellitus: Journal of King Saud University-Science; 2020.

  63. Oh J-Y, Barrett-Connor E. Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the rancho Bernardo study. Metabolism-Clinical and Experimental. 2002;51(3):356–9.

    Article  CAS  PubMed  Google Scholar 

  64. Rivera-Leon E-A, Palmeros-Sanchez B, Llama-Covarrubias IM, Fernandez S, Armendariz-Borunda J, Gonzalez-Hita M, et al. Vitamin-D receptor gene polymorphisms (TaqI and ApaI) and circulating osteocalcin in type 2 diabetic patients and healthy subjects. Endokrynologia Polska. 2015;66(4):329–33.

    Article  PubMed  Google Scholar 

  65. Ye W-Z, Reis AF, Dubois-Laforgue D, Bellanné-Chantelot C, Timsit J, Velho G. Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol. 2001;145(2):181–6.

    Article  CAS  PubMed  Google Scholar 

  66. Vural H, Maltas E. RT-qPCR assay on the vitamin D receptor gene in type 2 diabetes and hypertension patients in Turkey. Genet Mol Res. 2012;11(1):582–90.

    Article  CAS  PubMed  Google Scholar 

  67. Dilmec F, Uzer E, Akkafa F, Kose E, van Kuilenburg ABP. Detection of VDR gene ApaI and TaqI polymorphisms in patients with type 2 diabetes mellitus using PCR-RFLP method in a Turkish population. J Diabetes Complicat. 2010;24(3):186–91.

    Article  Google Scholar 

  68. Rahmadhani R, Zaharan NL, Mohamed Z, Moy FM, Jalaludin MY. The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country. PLoS One. 2017;12(6):e0178695.

    Article  PubMed  Google Scholar 

  69. Shah DB, et al. Investigation of the VDR gene polymorphism in unrelated gujarati group with and without diabetic mellitus type-2. RESEARCH JOURNAL OF PHARMACEUTICAL BIOLOGICAL AND CHEMICAL SCIENCES. 2015;6(4):465–8.

    CAS  Google Scholar 

  70. Speer G, Cseh K, Winkler G, Vargha P, Braun E, Takacs I, et al. Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity. Eur J Endocrinol. 2001;144(4):385–9.

    Article  CAS  PubMed  Google Scholar 

  71. SATTAR, N.A., Relationship of Apal VDR Gene Polymorphism to Type 2 Diabetes Mellitus in Pakistani Population.

  72. Norman AW. Receptors for 1α, 25 (OH) 2D3: past, present, and future. J Bone Miner Res. 1998;13(9):1360–9.

    Article  CAS  PubMed  Google Scholar 

  73. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lee S, Clark SA, Gill RK, Christakos S. 1, 25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology. 1994;134(4):1602–10.

    Article  CAS  PubMed  Google Scholar 

  75. Nemere I, Schwartz Z, Pedrozo H, Sylvia VL, Dean DD, Boyan BD. Identification of a membrane receptor for 1, 25-dihydroxyvitamin D3 which mediates rapid activation of protein kinase C. J Bone Miner Res. 1998;13(9):1353–9.

    Article  CAS  PubMed  Google Scholar 

  76. Ogunkolade B-W, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K, 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  PubMed  Google Scholar 

  77. Johnson JA, Grande JP, Roche PC, Kumar R. Immunohistochemical localization of the 1, 25 (OH) 2D3 receptor and calbindin D28k in human and rat pancreas. American Journal of Physiology-Endocrinology and Metabolism. 1994;267(3):E356–60.

    Article  CAS  Google Scholar 

  78. Ishida H, Norman AW. Demonstration of a high affinity receptor for 1, 25-dihydroxyvitamin D3 in rat pancreas. Mol Cell Endocrinol. 1988;60(2–3):109–17.

    Article  CAS  PubMed  Google Scholar 

  79. Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, et al. A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet. 1991;49(3):668–73.

    CAS  PubMed  Google Scholar 

  80. Hitman GA, Mannan N, McDermott MF, Aganna E, Ogunkolade BW, Hales CN, et al. Vitamin D receptor gene polymorphisms influence insulin secretion in Bangladeshi Asians. Diabetes. 1998;47(4):688–90.

    Article  CAS  PubMed  Google Scholar 

  81. Chiu KC, Chuang L-M, Yoon C. The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians. BMC Medical Genetics. 2001;2(1):2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Yu F, et al. The genetic polymorphisms in vitamin D receptor and the risk of type 2 diabetes mellitus: an updated meta-analysis. Asia Pac J Clin Nutr. 2016;25(3):614.

    CAS  PubMed  Google Scholar 

  83. Lu, S., et al., The associations between the polymorphisms of vitamin D receptor and coronary artery disease: a systematic review and meta-analysis. Medicine, 2016. 95(21).

Download references

Acknowledgements

We would like to thanks all researchers who dedicate their life for science.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Electronics and Communication Engineering, Al-ameen Engineering College (Autonomous), Erode, Tamil Nadu, 638 104, India

    Surendar Aravindhan

  2. College of Medicine, University of Babylon, Hillah, Iraq

    Mohammed Fadhil Mohammed Almasoody

  3. College of Medicine, University of Babylon, Babil, Iraq

    Nihad Abdallah Selman

  4. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation

    Alekhina Natalia Andreevna

  5. Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, Chennai, India

    Sahithya Ravali

  6. Department of Clinical Biochemistry, School of Medicine, Tarbiat Modares University, Tehran, Iran

    Payam Mohammadi

  7. Department of Hematology, School of Medicine, Tarbiat Modares University, Tehran, Iran

    Mohammad Masoud Eslami & Bahman Razi

  8. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Saeed Aslani

  9. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Danyal Imani

Authors
  1. Surendar Aravindhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed Fadhil Mohammed Almasoody
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nihad Abdallah Selman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alekhina Natalia Andreevna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sahithya Ravali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Payam Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammad Masoud Eslami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bahman Razi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Saeed Aslani
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Danyal Imani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PM and MA originated the study, acquired data. AA, ME and SR performed statistical analysis, interpreted data, drafted the manuscript. BR and SA revised the manuscript. BR and DI developed the main idea of the work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Surendar Aravindhan.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s note

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

Supplementary Information

ESM 1

(DOCX 4163 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aravindhan, S., Almasoody, M.F.M., Selman, N.A. et al. Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies. J Diabetes Metab Disord 20, 845–867 (2021). https://doi.org/10.1007/s40200-020-00704-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-020-00704-z

Keywords

Search

Navigation