Skip to main content

Advertisement

Log in

Vitamin D receptor FokI, TaqI, and ApaI polymorphisms and susceptibility to systemic lupus erythematosus: an updated meta-analysis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

This study aimed to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE). Meta-analyses were conducted to determine the associations between the VDR FokI, TaqI, and ApaI polymorphisms and SLE in all subjects and each ethnic group. A total of 12 studies were considered in the meta-analysis, which involved 1974 patients and 2506 controls. Meta-analysis of the VDR FokI polymorphism showed no association between SLE and the FokI F allele in all study subjects (OR = 1.047, 95% CI = 0.781–1.403, p = 0.758). However, the meta-analysis showed a significant association between SLE and the VDR FokI F allele in the Arab population (OR = 1.721, 95% CI = 1.417–2.088, p < 0.001). Analysis using the recessive and dominant models and homozygote contrast showed the same pattern for the VDR FokI F allele in Europeans, Asians, and Arabs. This meta-analysis showed that polymorphisms in VDR FokI, TaqI, and ApaI are not associated with SLE susceptibility in overall, European and Asian populations. However, the VDR FokI polymorphism is associated with SLE susceptibility in the Arab population.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kang SH, Chung BH, Choi SR, Lee JY, Park HS, Sun IO, Choi BS, Park CW, Kim YS, Yang CW Comparison of clinical outcomes by different renal replacement therapy in patients with end-stage renal disease secondary to lupus nephritis. Korean J Intern Med 26:60–67

  2. Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118:434–443

    Article  PubMed  Google Scholar 

  3. Maruotti N, Cantatore FP (2010) Vitamin D and the immune system. J Rheumatol 37:491–495

    Article  CAS  PubMed  Google Scholar 

  4. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980

    Article  CAS  PubMed  Google Scholar 

  5. Koizumi T, Nakao Y, Matsui T, Nakagawa T, Matsuda S, Komoriya K, Kanai Y, Fujita T (1985) Effects of corticosteroid and 1,24R-dihydroxy-vitamin D3 administration on lymphoproliferation and autoimmune disease in MRL/MP-lpr/lpr mice. Int Arch Allergy Appl Immunol 77:396–404

    Article  CAS  PubMed  Google Scholar 

  6. Sabio JM, Vargas-Hitos JA, Martinez-Bordonado J, Navarrete-Navarrete N, Díaz-Chamorro A, Olvera-Porcel C, Zamora M, Jiménez-Alonso J (2015) Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus. Lupus 24:155–163

    Article  CAS  PubMed  Google Scholar 

  7. Miyamoto K, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, Inoue Y, Morita K, Takeda E, Pike JW (1997) Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 11:1165–1179

    Article  CAS  PubMed  Google Scholar 

  8. Morrison NA, Yeoman R, Kelly PJ, Eisman JA (1992) Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci U S A 89:6665–6669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gado KH, Gado TH, Samie RMA, Khalil NM, Emam SL, Fouad HH (2016) Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients. The Egyptian Rheumatologist

  10. Mahto H, Tripathy R, Das BK, Panda AK (2017) Association between vitamin D receptor polymorphisms and systemic lupus erythematosus in an Indian cohort. Int J Rheum Dis 21:468–476. https://doi.org/10.1111/1756-185X.13245

    Article  PubMed  Google Scholar 

  11. Imam AA, Ibrahim HE, Farghaly MAA, Alkholy UM, Gawish HH, Abdalmonem N, Sherif AM, Ali YF, Hamed ME, Waked NM, Fathy MM, Khalil AM, Noah MA, Hegab MS, Ibrahim BR, Nabil RM, Fattah LA (2017) Vitamin D receptor gene FokI polymorphism in Egyptian children and adolescents with SLE: a case-control study. Lupus 26:1426–1434

    Article  CAS  PubMed  Google Scholar 

  12. Dzhebir G, Kamenarska Z, Hristova M, Savov A, Vinkov A, Kaneva R, Mitev V, Dourmishev L (2016) Association of vitamin D receptor gene BsmI B/b and FokI F/f polymorphisms with adult dermatomyositis and systemic lupus erythematosus. Int J Dermatol 55:e465–e468

    Article  PubMed  Google Scholar 

  13. Chen XE, Chen P, Chen SS, Lu J, Ma T, Shi G, Zhou Y, Li J, Sheng L (2017) A population association study of vitamin D receptor gene polymorphisms and haplotypes with the risk of systemic lupus erythematosus in a Chinese population. Immunol Res 65:750–756

    Article  CAS  PubMed  Google Scholar 

  14. Emerah AA, El-Shal AS (2013) Role of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D level in Egyptian female patients with systemic lupus erythematosus. Mol Biol Rep 40:6151–6162

    Article  CAS  PubMed  Google Scholar 

  15. Carvalho C, Marinho A, Leal B, Bettencourt A, Boleixa D, Almeida I, Farinha F, Costa PP, Vasconcelos C, Silva BM (2015) Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus 24:846–853

    Article  CAS  PubMed  Google Scholar 

  16. Mostowska A, Lianeri M, Wudarski M, Olesinska M, Jagodzinski PP (2013) Vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus. Mol Biol Rep 40:803–810

    Article  CAS  PubMed  Google Scholar 

  17. Monticielo OA, Teixeira Tde M, Chies JA, Brenol JC, Xavier RM (2012) Vitamin D and polymorphisms of VDR gene in patients with systemic lupus erythematosus. Clin Rheumatol 31:1411–1421

    Article  PubMed  Google Scholar 

  18. Luo XY, Wu LJ, Yang MH, Liu NT, Liao T, Tang Z, Zeng XF, Yuan GH (2011) Relationship of vitamin D receptor gene Fok I polymorphism with systemic lupus erythematosus. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 27:901–905

    CAS  PubMed  Google Scholar 

  19. Huang CM, Wu MC, Wu JY, Tsai FJ (2002) No association of vitamin D receptor gene start codon fok 1 polymorphisms in Chinese patients with systemic lupus erythematosus. J Rheumatol 29:1211–1213

    CAS  PubMed  Google Scholar 

  20. Bogaczewicz J, Kaleta B, Sysa-Jedrzejowska A, Robak E, Lukaszkiewicz J, Sitkiewicz D, Wozniacka A (2013) Vitamin D receptor gene polymorphism Fok I in the Polish population does not contribute to the risk of systemic lupus erythematosus. Lupus 22:750–751. https://doi.org/10.1177/0961203313482743

    Article  CAS  PubMed  Google Scholar 

  21. Monticielo OA, Brenol JC, Chies JA, Longo MG, Rucatti GG, Scalco R, Xavier RM (2012) The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus. Lupus 21:43–52

    Article  CAS  PubMed  Google Scholar 

  22. Abbasi M, Rezaieyazdi Z, Afshari JT, Hatef M, Sahebari M, Saadati N (2010) Lack of association of vitamin D receptor gene BsmI polymorphisms in patients with systemic lupus erythematosus. Rheumatol Int 30:1537–1539

    Article  CAS  PubMed  Google Scholar 

  23. Sakulpipatsin W, Verasertniyom O, Nantiruj K, Totemchokchyakarn K, Lertsrisatit P, Janwityanujit S (2006) Vitamin D receptor gene BsmI polymorphisms in Thai patients with systemic lupus erythematosus. Arthritis Res Ther 8:R48

    Article  PubMed  PubMed Central  Google Scholar 

  24. Csaszar A, Abel T (2001) Receptor polymorphisms and diseases. Eur J Pharmacol 414:9–22

    Article  CAS  PubMed  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  26. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  27. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  29. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38:3643–3651

    Article  CAS  PubMed  Google Scholar 

  31. Lee YH, Choi SJ, Ji JD, Song GG (2012) Vitamin D receptor ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis susceptibility: a meta-analysis. Mol Biol Rep 39:6471–6478

    Article  CAS  PubMed  Google Scholar 

  32. Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921

    Article  CAS  PubMed  Google Scholar 

  33. Luo XY, Yang MH, Wu FX, Wu LJ, Chen L, Tang Z, Liu NT, Zeng XF, Guan JL, Yuan GH (2012) Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population. Lupus 21:53–59

    Article  CAS  PubMed  Google Scholar 

  34. Mao S, Huang S (2014) Association between vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus: a meta-analysis. Rheumatol Int 34:381–388

    Article  CAS  PubMed  Google Scholar 

  35. Hu W, Niu G, Lin Y, Chen X, Lin L (2016) Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus: an updated meta-analysis. Clin Rheumatol 35:927–934

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by NRF-2017M3A9B4050335, Republic of Korea.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Young Ho Lee.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bae, SC., Lee, Y.H. Vitamin D receptor FokI, TaqI, and ApaI polymorphisms and susceptibility to systemic lupus erythematosus: an updated meta-analysis. Clin Rheumatol 37, 1529–1537 (2018). https://doi.org/10.1007/s10067-018-4036-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4036-z

Keywords

Navigation