Inflammation Research

, Volume 64, Issue 6, pp 463–470 | Cite as

A meta-analysis examining the association between the MUC5B rs35705950 T/G polymorphism and susceptibility to idiopathic pulmonary fibrosis

Original Research Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Objective

To explore whether the mucin (MUC) 5B rs35705950 T/G polymorphism confers susceptibility to idiopathic pulmonary fibrosis (IPF).

Methods

A meta-analysis was conducted to determine associations between the MUC5B rs35705950 T/G polymorphism and either IPF or connective tissue disease-associated interstitial lung disease (CTD-ILD). We used the allele contrast, recessive, dominant, and additive models. A total of 12 IPF studies comprising 2859 patients and 6901 controls and four CTD-ILD studies involving 903 patients and 3306 controls were included in the meta-analysis.

Results

There was a significant association between the Tallele of the MUC5B rs35705950 polymorphism and IPF in all subjects (OR 3.768, 95 % CI 2.935–4.836, p < 1.0 × 10−8). Analysis after stratification by ethnicity indicated that the Tallele was significantly associated with IPF in Europeans and Asians (OR 3.728, 95 % CI 2.858–4.863, p < 1.0 × 10−8; OR 4.334, 95 % CI 2.186–8.594, p = 2.6 × 10−6). However, there was no association between the Tallele and CTD-ILD in all subjects (OR 1.130, 95 % CI 0.937–1.363, p = 0.200), and in Europeans and Asians. Subgroup analysis by CTD type revealed no association between the Tallele and systemic sclerosis-associated ILD (SSc-ILD) and other CTD-ILDs.

Conclusions

The MUC5B rs35705950 T/G polymorphism confers susceptibility to IPF in Europeans and Asians, but is not associated with susceptibility to CTD-ILD.

Keywords

IPF MUC5B Polymorphism Meta-analysis 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors have no financial or non-financial conflicts of interest to declare.

References

  1. 1.
    Travis WD, King T Jr, Bateman E, Lynch D, Capron F, Colby T, et al. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2002;162:277–304.Google Scholar
  2. 2.
    Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61:980–5.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis. 2007;66:940–4.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45:613–20.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Thornton DJ, Devine PL, Hanski C, Howard M, Sheehan JK. Identification of two major populations of mucins in respiratory secretions. Am J Respir Crit Care Med. 1994;150:823–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Horimasu Y, Ohshimo S, Bonella F, Tanaka S, Ishikawa N, Hattori N, et al. MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology. 2015.Google Scholar
  8. 8.
    Wang C, Zhuang Y, Guo W, Cao L, Zhang H, Xu L, et al. Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males. PLoS One. 2014;9:e104919.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Wei R, Li C, Zhang M, Jones-Hall YL, Myers JL, Noth I, et al. Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes. Transl Res J Lab Clin Med. 2014;163:494–502.CrossRefGoogle Scholar
  10. 10.
    Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1:309–17.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Borie R, Crestani B, Dieude P, Nunes H, Allanore Y, Kannengiesser C, et al. The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population. PLoS One. 2013;8:e70621.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Stock CJ, Sato H, Fonseca C, Banya WA, Molyneaux PL, Adamali H, et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis. Thorax. 2013;68:436–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Zhang GY, Liao T, Gao WY. MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;365:178 Author reply 178–179.CrossRefPubMedGoogle Scholar
  15. 15.
    Lee YH, Rho YH, Choi SJ, Ji JD, Song GG. Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2006;27:157–61.CrossRefPubMedGoogle Scholar
  16. 16.
    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;38:3643–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Nath SK, Harley JB, Lee YH. Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet. 2005;118:225–34.CrossRefPubMedGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMedGoogle Scholar
  19. 19.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trial. 1986;7:177–88.CrossRefGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Putman RK, Rosas IO, Hunninghake GM. Genetics and early detection in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;189:770–8.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Santangelo S, Scarlata S, Zito A, Chiurco D, Pedone C, Incalzi RA. Genetic background of idiopathic pulmonary fibrosis. 2013.Google Scholar
  24. 24.
    Tansey D, Wells A, Colby T, Ip S, Nikolakoupolou A, Du Bois R, et al. Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis. Histopathology. 2004;44:585–96.CrossRefPubMedGoogle Scholar
  25. 25.
    Gregersen PK, Lee HS, Batliwalla F, Begovich AB. PTPN22: setting thresholds for autoimmunity. Semin Immunol. 2006;18:214–23.CrossRefPubMedGoogle Scholar
  26. 26.
    Peljto AL, Zhang Y, Fingerlin TE, Ma S-F, Garcia JG, Richards TJ, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013;309:2232–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Groshong S, Peljto A, Talbert J, McKean D, Markin C, Kidd R, et al. The MUC5B promoter polymorphism is associated with a less severe pathological form of familial interstitial pneumonia (FIP). Am J Respir Crit Care Med. 2012;185:A6865.Google Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal MedicineKorea University Anam Hospital, Korea University College of MedicineSeoulKorea

Personalised recommendations