Skip to main content

Advertisement

SpringerLink
Log in

5Apal, Taql, Fokl, and Bsml polymorphisms and the susceptibility of Behcet’s disease: an updated meta-analysis

  • Original Article
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Objective

The aim of this study was to investigate whether the gene polymorphisms of vitamin D receptor (VDR) had a genetic effect on the susceptibility of Behcet’s disease (BD).

Material and methods

We conducted a meta-analysis emphasizing the association between the VDR gene polymorphisms and the risk of BD. The strength of the association in five genetic models was assessed by pooled odds ratios (OR) with a corresponding 95%confidence interval (CI).

Results

A total of seven independent comparisons with 478 cases and 666 healthy controls were included in this meta-analysis. The overall results suggested that a significant association between ApaI polymorphism and BD risk was found in allele comparison, recessive model, and homozygote model among total populations. Subgroup analysis indicated that a significant association of ApaI polymorphism in the development of BD existed under the allelic model among Africans, while for Caucasians, a similar link was identified in the recessive model and homozygote model. Regarding Bsml polymorphism, an obvious relationship was detected to be significant in allele comparison and recessive model in the Caucasian population. Interestingly, the Fokl variant decreased the risk of BD in Africans under five genetic models, while it increased the risk in Caucasians across the recessive model and homozygote model.

Conclusion

The results of this meta-analysis provide evidence of the link between the four widely studied polymorphisms in the VDR gene and BD, indicating a robust estimate of the genetic risk.

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

Similar content being viewed by others

Availability of data

The data supporting this meta-analysis are from previously reported studies and datasets, which have been cited. The processed data are available from the corresponding author upon request.

References

  1. Kiafar M, Faezi ST, Kasaeian A, Baghdadi A, Kakaei S, Mousavi SA, Nejadhosseinian M, Shahram F, Ghodsi SZ, Shams H, Davatchi F. Diagnosis of Behcet’s disease: clinical characteristics, diagnostic criteria, and differential diagnoses. BMC Rheumatol. 2021;5(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yazici H, Seyahi E, Hatemi G, Yazici Y. Behcet syndrome: a contemporary view. Nat Rev Rheumatol. 2018;14(2):119.

    Article  PubMed  Google Scholar 

  3. Sazzini M, Garagnani P, Sarno S, De Fanti S, Lazzano T, Yang Yao D, Boattini A, Pazzola G, Maramotti S, Boiardi L, Franceschi C, Salvarani C, Luiselli D. Tracing Behcet’s disease origins along the Silk Road: an anthropological evolutionary genetics perspective. Clin Exp Rheumatol. 2015;33(6 Suppl 94):S60-6.

    PubMed  Google Scholar 

  4. Davatchi F, Shahram F, Chams-Davatchi C, Shams H, Nadji A, Akhlaghi M, Faezi T, Ghodsi Z, Faridar A, Ashofteh F, Sadeghi Abdollahi B. Behcet’s disease: from east to west. Clin Rheumatol. 2010;29(8):823–33.

    Article  PubMed  Google Scholar 

  5. Tursen U, Piskin G, Lotti T, Davatchi F. Pathological and immunological developments in Behcet’s disease. Patholog Res Int. 2012;2012:305780.

    PubMed  PubMed Central  Google Scholar 

  6. Mahmoudi M, Aslani S, Meguro A, Akhtari M, Fatahi Y, Mizuki N, Shahram F. A comprehensive overview on the genetics of Behcet's disease. Int Rev Immunol. 2022;41(2):84–106.

  7. Muhammad JS, Ishaq M, Ahmed K. Genetics and epigenetics mechanism in the pathogenesis of Behcet’s disease. Curr Rheumatol Rev. 2019;15(1):7–13.

    Article  CAS  PubMed  Google Scholar 

  8. Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D’Elios MM. Behcet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015;14(4):269–76.

    Article  PubMed  Google Scholar 

  9. Malek Mahdavi A, Khabbazi A, Yaaghoobian B, Ghojazadeh M, Agamohammadi R, Kheyrollahiyan A, Rashtchizadeh N. Cigarette smoking and risk of Behcet’s disease: a propensity score matching analysis. Mod Rheumatol. 2019;29(4):633–9.

    Article  PubMed  Google Scholar 

  10. Faezi ST, Ansari N, Paragomi P, Akhlaghi M, Ghanavat M, Davatchi F. Vitamin D deficiency in patients with Behcet’s disease. J Diabetes Metab Disord. 2014;13(1):18.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gul A. Genetics of Behcet’s disease: lessons learned from genomewide association studies. Curr Opin Rheumatol. 2014;26(1):56–63.

    Article  PubMed  Google Scholar 

  12. Sheikh V, Kasapoglu P, Zamani A, Basiri Z, Tahamoli-Roudsari A, Alahgholi-Hajibehzad M. Vitamin D3 inhibits the proliferation of T helper cells, downregulate CD4(+) T cell cytokines and upregulate inhibitory markers. Hum Immunol. 2018;79(6):439–45.

    Article  CAS  PubMed  Google Scholar 

  13. Alireza Khabbazi MG, Hajebrahimi S, Nikniaz Z. Relationship between vitamin D level and Bechcet’s disease activity: a systematic review and meta-analysis. Int J Vitam Nutr Res. 2020;90(5–6):527–34.

    Article  PubMed  Google Scholar 

  14. Bizzaro G, Antico A, Fortunato A, Bizzaro N. Vitamin D and autoimmune diseases: is vitamin D receptor (VDR) polymorphism the culprit? Isr Med Assoc J. 2017;19(7):438–43.

    PubMed  Google Scholar 

  15. Mestiri S, Zaaber I, Nasr I, Marmouch H. Implication of VDR Rs7975232 and FCGR2A Rs1801274 gene polymorphisms in the risk and the prognosis of autoimmune thyroid diseases in the Tunisian population. Balkan J Med Genet. 2020;23(1):69–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang WT, Jin TF, Chen L. Associations of four common VDR polymorphisms with rheumatoid arthritis and systemic lupus erythematosus: evidence from a meta-analysis. Lupus. 2020;29(4):364–70.

    Article  CAS  PubMed  Google Scholar 

  17. Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev. 2000;22(2):203–17.

    Article  CAS  PubMed  Google Scholar 

  18. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143–56.

    Article  CAS  PubMed  Google Scholar 

  19. van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, Overbergh L, Verstuyf A, Bouillon R, Roep BO, Badenhoop K, Mathieu C. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol. 2007;37(2):395–405.

    Article  PubMed  Google Scholar 

  20. Karray EF, Ben Dhifallah I, Ben Abdelghani K, Ben Ghorbel I, Khanfir M, Houman H, Hamzaoui K, Zakraoui L. Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behcet’s disease in Tunisians. Joint Bone Spine. 2012;79(2):144–8.

    Article  CAS  PubMed  Google Scholar 

  21. Kolahi S, Khabbazi A, Khodadadi H, Estiar MA, Hajialiloo M, Emrahi L, Sakhinia E. Vitamin D receptor gene polymorphisms in Iranian Azary patients with Behcet’s disease. Scand J Rheumatol. 2015;44(2):163–7.

    Article  CAS  PubMed  Google Scholar 

  22. Tizaoui K, Kaabachi W, Ouled Salah M, Ben Amor A, Hamzaoui A, Hamzaoui K. Vitamin D receptor TaqI and ApaI polymorphisms: a comparative study in patients with Behcet’s disease and rheumatoid arthritis in Tunisian population. Cell Immunol. 2014;290(1):66–71.

    Article  CAS  PubMed  Google Scholar 

  23. Erten G, Kalkan M, Bilgic Gazioglu S, Akdeniz N, Ozkok E, B Vural, TaqI, FokI, and ApaI polymorphisms in the vitamin D receptor in Behcet’s disease in Turkish population. Dis Markers 2016;2016 7475080.

  24. Kamal A, Gamal SM, Elgengehy FT, Alkemary AK, Siam I. Association of VDR ApaI and TaqI gene polymorphisms with the risk of scleroderma and Behcet’s disease. Immunol Invest. 2016;45(6):531–42.

    Article  CAS  PubMed  Google Scholar 

  25. Zeinab Al-Nahas MF, El Menyawi M, Shaker O, Ragab G. 25-Hydroxyvitamin D3 deficiency and vitamin D receptor polymorphisms in Egyptian patients with Behçet’s disease: a pilot study. Int J Clin Rheumatol. 2017;12(2):020–7.

    Google Scholar 

  26. Dal NE, Cerci P, Olmez U, Keskin G. The role of vitamin D receptor gene polymorphisms in the pathogenesis of Behcet’s disease: a case-control study in Turkish population. Ann Hum Genet. 2019;83(3):177–86.

    Article  CAS  PubMed  Google Scholar 

  27. Zahra Mirfeizi ST, Ravanshad Y, Hashemzadeh K, Kharazmi E, Mehrad-Majd H. Associations between vitamin D receptor polymorphisms and susceptibility to Behcet’s disease: a meta-analysis. Immunol Invest. 2018;47(4):389–402.

  28. Bowden J, Tierney JF, Copas AJ, Burdett S. Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics. BMC Med Res Methodol. 2011;11:41.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol. 2008;61(10):991–6.

    Article  PubMed  Google Scholar 

  31. Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000;53(11):1119–29.

    Article  CAS  PubMed  Google Scholar 

  32. Seydi Shirvania S. The molecular and clinical evidence of vitamin D signaling as a modulator of the immune system: role in Behçet’s disease. Immunol Lett. 2019;2019:10–9.

    Article  Google Scholar 

  33. Carlberg C, Campbell MJ. Vitamin D receptor signaling mechanisms: integrated actions of a well-defined transcription factor. Steroids. 2013;78(2):127–36.

    Article  CAS  PubMed  Google Scholar 

  34. Cutolo M, Otsa K, Paolino S, Yprus M, Veldi T, Seriolo B. Vitamin D involvement in rheumatoid arthritis and systemic lupus erythaematosus. Ann Rheum Dis. 2009;68(3):446–7.

    Article  CAS  PubMed  Google Scholar 

  35. Danyal Imani BR, Motallebnezhad M, Rezae R. Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. BMC Neurol. 2019;19(1):339.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tizaoui K KW, Hamzaoui A. Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies. Cell Mol Immunol. 2015;12:243–52.

    Article  PubMed  Google Scholar 

  37. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA. Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J Steroid Biochem Mol Biol. 2004;89–90(1–5):187–93.

    Article  PubMed  Google Scholar 

  38. Li L, Wu B, Liu JY, Yang LB. Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Arch Med Res. 2013;44(3):235–41.

    Article  PubMed  Google Scholar 

  39. Ogunkolade BW, Boucher BJ, Prahl JM, Bustin SA, Burrin JM, Noonan K, North BV, Mannan N, McDermott MF, DeLuca HF, Hitman GA. 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 

  40. Yun Zhang WX, Lu P, Yuan H. The association between VDR gene polymorphisms and diabetic retinopathy susceptibility: a systematic review and meta-analysis. Biomed Res Int. 2016;2016:5305282.

  41. Kalthoum Tizaoui KH. Association between VDR polymorphisms and rheumatoid arthritis disease: systematic review and updated meta-analysis of case-control studies. Immunobiology. 2015;220(6):807–16.

    Article  PubMed  Google Scholar 

  42. Neves JSF, Visentainer JEL, Reis D, Rocha Loures MA, Alves HV, Lara-Armi FF, de Alencar JB, Valentin Zacarias JM, Sell AM. The influence of vitamin D receptor gene polymorphisms in spondyloarthritis. Int J Inflam. 2020;2020 8880879

  43. Scherrer MAR, Rocha VB, Garcia LC. Behcet’s disease: review with emphasis on dermatological aspects. An Bras Dermatol. 2017;92(4):452–64.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation for Youth of China (Grant No. 81901765).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Mingxing Wu, Lanjiao Li, Lulu Tian, Danning Liu, Jia Jian, Yu Zhou & Yan Xu

Authors
  1. Mingxing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lanjiao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lulu Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danning Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia Jian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: W.M.X., X.Y., T.L.L., and J.J. Performed the experiments: W.M.X. and L.D.N. Analyzed the data: W.M.X. and L.L.J. Wrote the paper: W.M.X. and Z.Y. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yan Xu.

Ethics declarations

Ethics statement

This study does not involve human participants or animal subjects.

Conflict of interests

The authors declare that they have no conflict of interest.

Additional information

Publisher's note

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

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 27 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, M., Li, L., Tian, L. et al. 5Apal, Taql, Fokl, and Bsml polymorphisms and the susceptibility of Behcet’s disease: an updated meta-analysis. Immunol Res 70, 781–792 (2022). https://doi.org/10.1007/s12026-022-09306-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-022-09306-8

Keywords

Search

Navigation