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Vitamin D receptor FokI, BsmI, and TaqI polymorphisms and susceptibility to rheumatoid arthritis

A meta-analysis

FokI, BsmI und TaqI-Polymorphismus des Vitamin-D-Rezeptors und Anfälligkeit für rheumatoide Arthritis

Eine Metaanalyse

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Abstract

Objective

The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA).

Methods

Meta-analyses were conducted on the associations between the VDR FokI, BsmI, and TaqI polymorphisms and RA.

Results

A total of seven studies were considered in the meta-analysis, involving a total of 923 patients and 912 controls. Meta-analysis of the VDR FokI polymorphism showed no association between RA and the F allele in the entire studied cohort (odds ratio, OR = 1.1740, 95 % confidence interval, CI = 0.994–1.387, p = 0.059). However, stratification by ethnicity revealed a significant association between the F allele and RA in Europeans (OR = 1.402, 95 % CI = 1.126–1.746, p = 0.003). Furthermore, an association was found between RA and the VDR FokI polymorphism using both the dominant model and homozygote contrast. Meta-analysis revealed no association between RA and the VDR BsmI B and TaqI T polymorphisms in Europeans (OR for the B allele = 1.065, 95 % CI = 0.911–1.245, p = 0.427; OR for the T allele = 1.065, 95 % CI = 0.834–1.361, p = 0.613).

Conclusion

This meta-analysis suggests that the VDR FokI polymorphism is associated with susceptibility to RA in European populations.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es zu untersuchen, ob Vitamin-D-Rezeptor(VDR)-Polymorphismen mit der Anfälligkeit für rheumatoide Arthritis (RA) in Zusammenhang stehen.

Methoden

Es wurden Metaanalysen zu den Assoziationen zwischen den FokI-, BsmI- und TaqI-Polymorphismen des VDR und RA durchgeführt.

Ergebnisse

In der Metaanalyse wurden 7 Studien berücksichtigt, die 923 Patienten und 912 Kontrollen umfassten. Die Metaanalyse des VDR-FokI-Polymorphismus ergab keine Assoziation zwischen RA und dem F-Allel in der gesamten untersuchten Kohorte (Odds Ratio, OR = 1,1740; 95 %-Konfidenzintervall, 95%-KI = 0,994–1,387; p = 0,059). Jedoch zeigte die Stratifizierung nach Ethnizität eine signifikante Assoziation zwischen dem F-Allel und RA bei Europäern (OR = 1,402; 95 %-KI = 1,126–1,746; p = 0,003). Darüber hinaus wurde eine Assoziation zwischen RA und dem VDR-FokI-Polymorphismus anhand des dominanten Modells und des homozygoten Kontrasts festgestellt. Wie die Metaanalyse zeigte, bestand keine Assoziation zwischen RA und den VDR-BsmI-B- und -TaqI-T-Polymorphismen bei Europäern (OR für das B-Allel = 1,065; 95 %-KI = 0,911–1,245; p = 0,427; OR für das T-Allel = 1,065; 95 %-KI = 0,834–1,361; p = 0,613).

Schlussfolgerung

Die vorliegende Metaanalyse liefert Hinweise darauf, dass der VDR-FokI-Polymorphismus mit der Anfälligkeit für RA in der europäischen Bevölkerung assoziiert ist.

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References

  1. MacGregor AJ, Snieder H, Rigby AS et al (2000) Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 43(1):30–37

    Article  CAS  PubMed  Google Scholar 

  2. Kim HR, Park MK, Cho ML et al (2010) Induction of macrophage migration inhibitory factor in ConA-stimulated rheumatoid arthritis synovial fibroblasts through the P38 map kinase-dependent signaling pathway. Korean J Intern Med 25(3):317–326

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Boonstra A, Barrat FJ, Crain C et al (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167(9):4974–4980

    Article  CAS  PubMed  Google Scholar 

  5. Koizumi T, Nakao Y, Matsui T et al (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(4):396–404

    Article  CAS  PubMed  Google Scholar 

  6. Miyamoto K, Kesterson RA, Yamamoto H et al (1997) Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 11(8):1165–1179

    Article  CAS  PubMed  Google Scholar 

  7. 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(15):6665–6669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Karray EF, Ben Dhifallah I, Ben Abdelghani K et al (2012) Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behcet’s disease in Tunisians. Joint Bone Spine 79(2):144–148

    Article  CAS  PubMed  Google Scholar 

  9. Maalej A, Petit-Teixeira E, Michou L et al (2005) Association study of VDR gene with rheumatoid arthritis in the French population. Genes Immun 6(8):707–711

    CAS  PubMed  Google Scholar 

  10. Goertz B, Fassbender WJ, Williams JC et al (2003) Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients. Clin Exp Rheumatol 21(3):333–339

    CAS  PubMed  Google Scholar 

  11. Garcia-Lozano JR, Gonzalez-Escribano MF, Valenzuela A et al (2001) Association of vitamin D receptor genotypes with early onset rheumatoid arthritis. Eur J Immunogenet 28(1):89–93

    Article  CAS  PubMed  Google Scholar 

  12. Ranganathan P (2009) Genetics of bone loss in rheumatoid arthritis—role of vitamin D receptor polymorphisms. Rheumatology (Oxford) 48(4):342–346

  13. Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118(2):225–234

    Article  CAS  PubMed  Google Scholar 

  14. Lee YH, Witte T, Momot T et al (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52(12):3966–3974

    Article  CAS  PubMed  Google Scholar 

  15. Lee YH, Ji JD, Song GG (2007) Tumor necrosis factor-alpha promoter − 308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis. J Rheumatol 34(1):43–49

    CAS  PubMed  Google Scholar 

  16. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  17. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  19. Clark MF, Baudouin SV (2006) A systematic review of the quality of genetic association studies in human sepsis. Intensive Care Med 32(11):1706–1712

    Article  PubMed  Google Scholar 

  20. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hitchon CA, Sun Y, Robinson DB et al (2012) Vitamin D receptor polymorphism rs2228570 (Fok1) is associated with rheumatoid arthritis in North American natives. J Rheumatol 39(9):1792–1797

    Article  CAS  PubMed  Google Scholar 

  22. Hussien YM, Shehata A, Karam RA et al (2013) Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthritis patients with and without osteoporosis. Mol Biol Rep 40(5):3675–3680

    Article  CAS  PubMed  Google Scholar 

  23. Rass P, Pakozdi A, Lakatos P et al (2006) Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. Rheumatol Int 26(11):964–971

    Article  CAS  PubMed  Google Scholar 

  24. Lee CK, Hong JS, Cho YS et al (2001) Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis. J Korean Med Sci 16(2):188–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Milchert M (2010) Association between BsmI vitamin D receptor gene polymorphism and serum concentration of vitamin D with progression of rheumatoid arthritis. Ann Acad Med Stetin 56(1):45–56

    CAS  PubMed  Google Scholar 

  26. Raychaudhuri S (2010) Recent advances in the genetics of rheumatoid arthritis. Curr Opin Rheumatol 22(2):109–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee YH, Bae SC, Choi SJ et al (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651

    Article  CAS  PubMed  Google Scholar 

  28. 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(6):6471–6478

    Article  CAS  PubMed  Google Scholar 

  29. Arai H, Miyamoto K, Taketani Y et al (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(6):915–921

    Article  CAS  PubMed  Google Scholar 

  30. Monticielo OA, Brenol JC, Chies JA et al (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(1):43–52

    Article  CAS  PubMed  Google Scholar 

  31. Luo XY, Yang MH, Wu FX et al (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(1):53–59

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).

Compliance with ethical guidelines

Conflict of interest. G.G. Song, S.-C. Bae, and Y.H. Lee state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, 136–705, Seoul, Korea

    G.G. Song & Y.H. Lee MD, PhD

  2. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

    S.-C. Bae

Authors
  1. G.G. Song
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  2. S.-C. Bae
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  3. Y.H. Lee MD, PhD
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Corresponding author

Correspondence to Y.H. Lee MD, PhD.

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Song, G., Bae, SC. & Lee, Y. Vitamin D receptor FokI, BsmI, and TaqI polymorphisms and susceptibility to rheumatoid arthritis. Z Rheumatol 75, 322–329 (2016). https://doi.org/10.1007/s00393-015-1581-6

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  • DOI: https://doi.org/10.1007/s00393-015-1581-6

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