Skip to main content

Advertisement

SpringerLink
Log in

Association between FCGR3B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

This study determined whether FCGR3B copy number variations (CNVs) were associated with susceptibility to autoimmune diseases.

Methods

A meta-analysis was conducted to determine the association between FCGR3B CNVs and susceptibility to autoimmune diseases by comparing low FCGR3B CN (<2 to ≥2) and high FCGR3B CN (>2 to ≤2).

Results

In all, 28 comparative studies from 15 reports involving 12,160 patients and 11,103 controls were included in this meta-analysis. The meta-analysis showed a significant association between low FCGR3B CN and autoimmune diseases (OR = 1.496, 95 % CI = 1.301–1.716, p = 1.0 × 10−9). Subgroup analysis according to ethnicity indicated an association between low FCGR3B CN and autoimmune diseases in Caucasians (OR = 1.482, 95 % CI = 1.219–1.801, p = 7.7 × 10−6) and Asians (OR = 1.498, 95 % CI = 1.306–1.717, p = 1.0 × 10−9). Meta-analysis according to the type of autoimmune disease indicated a significant association of low FCGR3B CN with systemic lupus erythematosus (SLE; OR = 1.797, 95 % CI = 1.562–2.068, p < 1.0 × 10−9), primary Sjogren’s syndrome (pSS; OR = 2.263, 95 % CI = 1.316–3.892, p = 0.003), and Wegener’s granulomatosis (WG; OR = 1.973, 95 % CI = 1.178–3.302, p = 0.010), but not with rheumatoid arthritis (RA; OR = 1.333, 95 % CI = 0.947–1.877, p = 0.099). However, the meta-analysis showed no association between high FCGR3B CN and SLE, RA, pSS, and WG.

Conclusions

Thus, the results of this meta-analysis indicated that low FCGR3B CN increased susceptibility to autoimmune diseases, especially SLE, pSS, and WG.

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

Similar content being viewed by others

References

  1. Marrack P, Kappler J, Kotzin BL. Autoimmune disease: why and where it occurs. Nat Med. 2001;7(8):899–905.

    Article  CAS  PubMed  Google Scholar 

  2. Becker KG. The common variants/multiple disease hypothesis of common complex genetic disorders. Med Hypotheses. 2004;62(2):309–17.

    Article  CAS  PubMed  Google Scholar 

  3. Becker KG. Comparative genetics of type 1 diabetes and autoimmune disease: common loci, common pathways? Diabetes. 1999;48(7):1353–8.

    Article  CAS  PubMed  Google Scholar 

  4. Li X, Howard TD, Zheng SL, Haselkorn T, Peters SP, Meyers DA, et al. Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J Allergy Clin Immunol 2010;125(2):328–35 e11.

  5. Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol. 2001;19:275–90.

    Article  CAS  PubMed  Google Scholar 

  6. Su K, Wu J, Edberg JC, McKenzie SE, Kimberly RP. Genomic organization of classical human low-affinity Fcgamma receptor genes. Genes Immun. 2002;3(Suppl 1):S51–6.

    Article  CAS  PubMed  Google Scholar 

  7. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford). 2006;45(2):166–70.

    Article  CAS  Google Scholar 

  8. Lee YH, Nath SK. Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet. 2005;118(3–4):434–43.

    Article  PubMed  Google Scholar 

  9. Brown EE, Edberg JC, Kimberly RP. Fc receptor genes and the systemic lupus erythematosus diathesis. Autoimmunity. 2007;40(8):567–81.

    Article  CAS  PubMed  Google Scholar 

  10. Yim S-H, Jung S-H, Chung B, Chung Y-J. Clinical implications of copy number variations in autoimmune disorders. Korean J Intern Med. 2015;30(3):294–304.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Breunis WB, van Mirre E, Geissler J, Laddach N, Wolbink G, van der Schoot E, et al. Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Hum Mutat. 2009;30(5):E640–50.

    Article  PubMed  Google Scholar 

  12. Mayadas TN, Tsokos GC, Tsuboi N. Mechanisms of immune complex–mediated neutrophil recruitment and tissue injury. Circulation. 2009;120(20):2012–24.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Nimmerjahn F, Ravetch JV. Fcγ receptors as regulators of immune responses. Nat Rev Immunol. 2008;8(1):34–47.

    Article  CAS  PubMed  Google Scholar 

  14. Willcocks LC, Lyons PA, Clatworthy MR, Robinson JI, Yang W, Newland SA, et al. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. J Exp Med. 2008;205(7):1573–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Salmon JE, Pricop L. Human receptors for immunoglobulin G: key elements in the pathogenesis of rheumatic disease. Arthritis Rheum. 2001;44(4):739–50.

    Article  CAS  PubMed  Google Scholar 

  16. Chen JY, Wang CM, Chang SW, Cheng CH, Wu YJ, Lin JC, et al. Association of FCGR3A and FCGR3B copy number variations with systemic lupus erythematosus and rheumatoid arthritis in Taiwanese patients. Arthritis Rheumatol. 2014;66(11):3113–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Dunstan E, Lester S, Black R, Rischmueller M, Chan H, Hewitt AW, et al. No Association between FC gamma R3B copy number variation and susceptibility to biopsy-proven giant cell arteritis. Arthritis. 2013;2013:514914.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Asano K, Matsumoto T, Umeno J, Hirano A, Esaki M, Hosono N, et al. Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis. Inflamm Bowel Dis. 2013;19(10):2061–8.

    Article  PubMed  Google Scholar 

  19. Nossent JC, Rischmueller M, Lester S. Low copy number of the Fc-gamma receptor 3B gene FCGR3B is a risk factor for primary Sjogren’s syndrome. J Rheumatol. 2012;39(11):2142–7.

    Article  CAS  PubMed  Google Scholar 

  20. Black R, Lester S, Dunstan E, Shahram F, Nadji A, Bayat N, et al. Fc-gamma receptor 3B copy number variation is not a risk factor for Behcet’s disease. Int J Rheumatol. 2012;2012:167096.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Graf SW, Lester S, Nossent JC, Hill CL, Proudman SM, Lee A, et al. Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis. Arthritis Res Ther. 2012;14(1):R28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. McKinney C, Broen JC, Vonk MC, Beretta L, Hesselstrand R, Hunzelmann N, et al. Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis. Genes Immun. 2012;13(6):458–60.

    Article  CAS  PubMed  Google Scholar 

  23. Molokhia M, Fanciulli M, Petretto E, Patrick AL, McKeigue P, Roberts AL, et al. FCGR3B copy number variation is associated with systemic lupus erythematosus risk in Afro-Caribbeans. Rheumatology (Oxford). 2011;50(7):1206–10.

    Article  CAS  Google Scholar 

  24. Marques RB, Thabet MM, White SJ, Houwing-Duistermaat JJ, Bakker AM, Hendriks GJ, et al. Genetic variation of the Fc gamma receptor 3B gene and association with rheumatoid arthritis. PLoS One. 2010;5(10):e13173.

    Article  PubMed Central  PubMed  Google Scholar 

  25. McKinney C, Fanciulli M, Merriman ME, Phipps-Green A, Alizadeh BZ, Koeleman BP, et al. Association of variation in Fcgamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples. Ann Rheum Dis. 2010;69(9):1711–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Zhou XJ, Lv JC, Bu DF, Yu L, Yang YR, Zhao J, et al. Copy number variation of FCGR3A rather than FCGR3B and FCGR2B is associated with susceptibility to anti-GBM disease. Int Immunol. 2010;22(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  27. Fanciulli M, Norsworthy PJ, Petretto E, Dong R, Harper L, Kamesh L, et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet. 2007;39(6):721–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Niederer HA, Willcocks LC, Rayner TF, Yang W, Lau YL, Williams TN, et al. Copy number, linkage disequilibrium and disease association in the FCGR locus. Hum Mol Genet. 2010;19(16):3282–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Breunis WB, van Mirre E, Bruin M, Geissler J, de Boer M, Peters M, et al. Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood. 2008;111(3):1029–38.

    Article  CAS  PubMed  Google Scholar 

  30. Mamtani M, Anaya J, He W, Ahuja S. Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases. Genes Immun. 2010;11(2):155–60.

    Article  CAS  PubMed  Google Scholar 

  31. Yuan J, Zhao D, Wu L, Xu X, Pang Y, Zhang J, et al. FCGR3B copy number loss rather than gain is a risk factor for systemic lupus erythematous and lupus nephritis: a meta-analysis. Int J Rheum Dis. 2015;18(4):392–7.

    Article  CAS  PubMed  Google Scholar 

  32. McKinney C, Merriman TR. Meta-analysis confirms a role for deletion in FCGR3B in autoimmune phenotypes. Hum Mol Genet. 2012;21(10):2370–6.

    Article  CAS  PubMed  Google Scholar 

  33. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep. 2010;37(1):227–34.

    Article  CAS  PubMed  Google Scholar 

  34. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG. Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep. 2011;38(6):3643–51.

    Article  CAS  PubMed  Google Scholar 

  35. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG. PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int. 2007;27(9):827–33.

    Article  CAS  PubMed  Google Scholar 

  36. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

    Article  PubMed  Google Scholar 

  37. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  38. 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  PubMed Central  CAS  PubMed  Google Scholar 

  39. Morris DL, Roberts AL, Witherden AS, Tarzi R, Barros P, Whittaker JC, et al. Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus. Eur J Hum Genet. 2010;18(9):1027–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Robinson JI, Carr IM, Cooper DL, Rashid LH, Martin SG, Emery P, et al. Confirmation of association of FCGR3B but not FCGR3A copy number with susceptibility to autoantibody positive rheumatoid arthritis. Hum Mutat. 2012;33(4):741–9.

    Article  CAS  PubMed  Google Scholar 

  41. Bournazos S, Bournazou I, Murchison JT, Wallace WA, McFarlane P, Hirani N, et al. Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis. Respiration. 2011;81(2):142–9.

    Article  PubMed  Google Scholar 

  42. Niederer HA, Willcocks LC, Rayner TF, Yang W, Lau YL, Williams TN, et al. Copy number, linkage disequilibrium and disease association in the FCGR locus. Human Mol Genet. 2010;19(16):3282–94.

    Article  CAS  Google Scholar 

  43. Harper L, Savage C. Pathogenesis of ANCA-associated systemic vasculitis. J Pathol. 2000;190(3):349–59.

    Article  CAS  PubMed  Google Scholar 

  44. Ierino F, Powell M, McKenzie I, Hogarth P. Recombinant soluble human Fc gamma RII: production, characterization, and inhibition of the Arthus reaction. J Exp Med. 1993;178(5):1617–28.

    Article  CAS  PubMed  Google Scholar 

  45. Galon J, Paulet P, Galinha A, Lores P, Bonnerot C, Jami J, et al. Soluble Fcγ receptors: interaction with ligands and biological consequences. Int Rev Immunol. 1997;16(1–2):87–111.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 72 Inchon-ro, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee, Young Ho Seo, Jae-Hoon Kim, Sung Jae Choi, Jong Dae Ji & Gwan Gyu Song

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

    Sang-Cheol Bae

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sang-Cheol Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Ho Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jae-Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung Jae Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jong Dae Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Additional information

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, Y.H., Bae, SC., Seo, Y.H. et al. Association between FCGR3B copy number variations and susceptibility to autoimmune diseases: a meta-analysis. Inflamm. Res. 64, 983–991 (2015). https://doi.org/10.1007/s00011-015-0882-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-015-0882-1

Keywords

Search

Navigation