https://doi.org/10.4081/monaldi.2024.2952
Gene polymorphisms and risk of idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Submitted: February 13, 2024
Accepted: September 9, 2024
Published: October 29, 2024
Accepted: September 9, 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Idiopathic pulmonary fibrosis (IPF) has been widely hypothesized to occur as a result of an interplay between a nexus of environmental and genetic risk factors. However, not much is known about the genetic aspect of this disease. The objective of this review was to identify the genetic polymorphisms associated with the risk of developing IPF. We searched PubMed, EBSCO CINAHL Plus, Web of Science, and Wiley Cochrane Library databases for studies on risk factors of IPF published between March 2000 and November 2023. Studies with an IPF diagnosis based only on the American Thoracic Society and the European Respiratory Society guidelines were included. Thirty-one case-control studies were included with 3997 IPF and 20,925 non-IPF subjects. Two of the studies enrolled biopsy-proven IPF patients; 13 studies diagnosed IPF on the basis of clinical and high-resolution computed tomography (HRCT) findings; and 14 studies diagnosed based on both biopsy and clinical and HRCT findings. 16 studies with MUC5B rs35705950, IL-4 rs2243250, IL-4 rs2070874, and tumor necrosis factor α (TNFα)-308 were eligible for meta-analysis. The allele contrast model (T versus G) for MUC5B rs35705950 revealed statistically significant association of T allele with the risk of IPF [odds ratio (OR) 3.84, 95% confidence interval (CI) 3.20 to 4.61, adjusted p<0.0001), as was the allele contrast model for Asian (OR 2.83, 95% CI 1.51 to 5.32, adjusted p=0.009) and Caucasian (OR 4.11, 95% CI 3.56 to 4.75, adjusted p<0.0001). The allele contrast models for IL-4 rs2243250, IL-4 rs2070874, and TNFα-308 did not demonstrate any significant association with IPF. This review suggests an association of MUC5B rs35705950 T allele with the risk of developing IPF. To our knowledge, this study is the first to aggregate several genetic polymorphisms associated with IPF.
Nakamura Y, Suda T. Idiopathic pulmonary fibrosis: diagnosis and clinical manifestations. Clin Med Insights Circ Respir Pulm Med 2015;9:163-71.
DOI: https://doi.org/10.4137/CCRPM.S39897
Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161:646-64.
DOI: https://doi.org/10.1164/ajrccm.161.2.ats3-00
Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2018;198:e44-68.
DOI: https://doi.org/10.1164/rccm.201807-1255ST
Salton F, Ruaro B, Confalonieri P, Confalonieri M. Epithelial–mesenchymal transition: a major pathogenic driver in idiopathic pulmonary fibrosis? Medicina 2020;56:608.
DOI: https://doi.org/10.3390/medicina56110608
Jia Q, Lei Y, Chen S, et al. Circulating inflammatory cytokines and risk of idiopathic pulmonary fibrosis: a Mendelian randomization study. BMC Pulm Med 2023;23:369.
DOI: https://doi.org/10.1186/s12890-023-02658-3
Huang D, Gong L, Wu Z, et al. Genetic association of circulating adipokines with risk of idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study. Lung 2023;201:355-62.
DOI: https://doi.org/10.1007/s00408-023-00640-8
Park Y, Ahn C, Kim TH. Occupational and environmental risk factors of idiopathic pulmonary fibrosis: a systematic review and meta-analyses. Sci Rep 2021;11:4318.
DOI: https://doi.org/10.1038/s41598-021-81591-z
Steele MP, Speer MC, Loyd JE, et al. Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med 2005;172:1146-52.
DOI: https://doi.org/10.1164/rccm.200408-1104OC
Baratella E, Ruaro B, Giudici F, et al. Evaluation of correlations between genetic variants and high-resolution computed tomography patterns in idiopathic pulmonary fibrosis. Diagnostics 2021;11:762.
DOI: https://doi.org/10.3390/diagnostics11050762
Borie R, Crestani B, Dieude P, 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.
DOI: https://doi.org/10.1371/journal.pone.0070621
Moorsel CHMv, Oosterhout MFMv, Barlo NP, et al. Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a Dutch cohort. Am J Respir Crit Care Med 2010;182:1419-25.
DOI: https://doi.org/10.1164/rccm.200906-0953OC
Alder JK, Chen JJ-L, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A 2008;105:13051-6.
DOI: https://doi.org/10.1073/pnas.0804280105
Wu X, Li W, Luo Z, Chen Y. The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis. Sci Rep 2021;11:24007.
DOI: https://doi.org/10.1038/s41598-021-03533-z
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
DOI: https://doi.org/10.1371/journal.pmed.1000097
Zubairi ABS, Hassan M, Ali AS, et al. Risk factors associated with idiopathic pulmonary fibrosis: a systematic review and meta-analyses. PROSPERO. 2020.
American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002;165:277-304.
DOI: https://doi.org/10.1164/ajrccm.165.2.ats01
Raghu G. Idiopathic pulmonary fibrosis: guidelines for diagnosis and clinical management have advanced from consensus-based in 2000 to evidence-based in 2011. Eur Respir J 2011;37:743-6.
DOI: https://doi.org/10.1183/09031936.00017711
Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF)--practical implications. Respir Res 2013;14 Suppl 1:S2.
DOI: https://doi.org/10.1186/1465-9921-14-S1-S2
Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 2015;192:e3-19.
DOI: https://doi.org/10.1164/rccm.201506-1063ST
Wells G, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Martorell-Marugan J, Toro-Dominguez D, Alarcon-Riquelme ME, Carmona-Saez P. MetaGenyo: a web tool for meta-analysis of genetic association studies. BMC Bioinformatics 2017;18:563.
DOI: https://doi.org/10.1186/s12859-017-1990-4
Horimasu Y, Ohshimo S, Bonella F, et al. MUC 5 B promoter polymorphism in J apanese patients with idiopathic pulmonary fibrosis. Respirology 2015;20:439-44.
DOI: https://doi.org/10.1111/resp.12466
Jiang H, Hu Y, Shang L, et al. Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis. Int J Clin Exp Pathol 2015;8:14953-8.
Kishore A, Žižková V, Kocourková L, et al. Association study for 26 candidate loci in idiopathic pulmonary fibrosis patients from four European populations. Front Immunol 2016;7:274.
DOI: https://doi.org/10.3389/fimmu.2016.00274
Stock CJ, Sato H, Fonseca C, 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.
DOI: https://doi.org/10.1136/thoraxjnl-2012-201786
van der Vis JJ, Snetselaar R, Kazemier KM, et al. Effect of M uc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias. Respirology 2016;21:712-7.
DOI: https://doi.org/10.1111/resp.12728
Vasakova M, Striz I, Slavcev A, et al. Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis. Tissue Antigens 2006;67:229-32.
DOI: https://doi.org/10.1111/j.1399-0039.2006.00560.x
Ahn MH, Park BL, Lee SH, et al. A promoter SNP rs4073T> A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode. Respir Res 2011;12:73.
DOI: https://doi.org/10.1186/1465-9921-12-73
Aquino-Galvez A, Pérez-Rodríguez M, Camarena Á, et al. MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility. Hum Genet 2009;125:639-48.
DOI: https://doi.org/10.1007/s00439-009-0666-1
Aquino-Gálvez A, González-Ávila G, Pérez-Rodríguez M, et al. Analysis of heat shock protein 70 gene polymorphisms Mexican patients with idiopathic pulmonary fibrosis. BMC Pulm Med 2015;15:129.
DOI: https://doi.org/10.1186/s12890-015-0127-7
Bournazos S, Bournazou I, Murchison JT, et al. Fcγ receptor IIIb (CD16b) polymorphisms are associated with susceptibility to idiopathic pulmonary fibrosis. Lung 2010;188:475-81.
DOI: https://doi.org/10.1007/s00408-010-9262-3
Bournazos S, Bournazou I, Murchison JT, et al. Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis. Respiration 2011;81:142-9.
DOI: https://doi.org/10.1159/000321997
Checa M, Ruiz V, Montaño M, et al. MMP-1 polymorphisms and the risk of idiopathic pulmonary fibrosis. Hum Genet 2008;124:465-72.
DOI: https://doi.org/10.1007/s00439-008-0571-z
Peljto AL, Selman M, Kim DS, et al. The MUC5B promoter polymorphism is associated with idiopathic pulmonary fibrosis in a Mexican cohort but is rare among Asian ancestries. Chest 2015;147:460-4.
DOI: https://doi.org/10.1378/chest.14-0867
Riha R, Yang I, Rabnott G, et al. Cytokine gene polymorphisms in idiopathic pulmonary fibrosis. Intern Med J 2004;34:126-9.
DOI: https://doi.org/10.1111/j.1444-0903.2004.00503.x
Selman M, Lin H-M, Montaño M, et al. Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis. Hum Genet 2003;113:542-50.
DOI: https://doi.org/10.1007/s00439-003-1015-4
Uh ST, Kim TH, Shim EY, et al. Angiotensin-converting enzyme (ACE) gene polymorphisms are associated with idiopathic pulmonary fibrosis. Lung 2013;191:345-51.
DOI: https://doi.org/10.1007/s00408-013-9469-1
Uh ST, Jang AS, Park SW, et al. ADAM33 gene polymorphisms are associated with the risk of idiopathic pulmonary fibrosis. Lung 2014;192:525-32.
DOI: https://doi.org/10.1007/s00408-014-9578-5
Xaubet A, Fu W, Li M, et al. A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2010;27:121-30.
Zhang J, Xu D, Xu K, et al. HLA-A and HLA-B gene polymorphism and idiopathic pulmonary fibrosis in a Han Chinese population. Respir Med 2012;106:1456-62.
DOI: https://doi.org/10.1016/j.rmed.2012.06.015
Zorzetto M, Ferrarotti I, Trisolini R, et al. Complement receptor 1 gene polymorphisms are associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2003;168:330-4.
DOI: https://doi.org/10.1164/rccm.200302-221OC
Bonella F, Campo I, Zorzetto M, et al. Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF. Orphanet J Rare Dis 2021;16:111.
DOI: https://doi.org/10.1186/s13023-021-01750-3
Helling BA, Gerber AN, Kadiyala V, et al. Regulation of MUC5B expression in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 2017;57:91-9.
DOI: https://doi.org/10.1165/rcmb.2017-0046OC
Son JY, Kim SY, Cho SH, et al. TGF-β1 T869C polymorphism may affect susceptibility to idiopathic pulmonary fibrosis and disease severity. Lung 2013;191:199-205.
DOI: https://doi.org/10.1007/s00408-012-9447-z
Stock CJ, Conti C, Montero-Fernandez Á, et al. Interaction between the promoter MUC5B polymorphism and mucin expression: is there a difference according to ILD subtype? Thorax 2020;75:901-3.
DOI: https://doi.org/10.1136/thoraxjnl-2020-214579
Wang C, Zhuang Y, Guo W, et al. Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males. PloS One 2014;9:e104919.
DOI: https://doi.org/10.1371/journal.pone.0104919
Wei R, Li C, Zhang M, et al. Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes. Transl Res 2014;163:494-502.
DOI: https://doi.org/10.1016/j.trsl.2013.12.006
Zhang Y, Noth I, Garcia JG, Kaminski N. A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis. N Engl J Med 2011;364:1576-7.
DOI: https://doi.org/10.1056/NEJMc1013504
Zhang H-P, Zou J, Xie P, et al. Association of HLA and cytokine gene polymorphisms with idiopathic pulmonary fibrosis. Kaohsiung J Med Sci 2015;31:613-20.
DOI: https://doi.org/10.1016/j.kjms.2015.10.007
Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013;45:613-20.
DOI: https://doi.org/10.1038/ng.2609
Barros A, Oldham J, Noth I. Genetics of idiopathic pulmonary fibrosis. Am J Med Sci 2019;357:379-83.
DOI: https://doi.org/10.1016/j.amjms.2019.02.009
Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 2012;21:355-61.
DOI: https://doi.org/10.1183/09059180.00002512
Lee MG, Lee YH. A meta-analysis examining the association between the MUC5B rs35705950 T/G polymorphism and susceptibility to idiopathic pulmonary fibrosis. Inflamm Res 2015;64:463-70.
DOI: https://doi.org/10.1007/s00011-015-0829-6
Noth I, Zhang Y, Ma SF, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med 2013;1:309-17.
DOI: https://doi.org/10.1016/S2213-2600(13)70045-6
Allen RJ, Porte J, Braybrooke R, et al. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respir Med 2017;5:869-80.
DOI: https://doi.org/10.1016/S2213-2600(17)30387-9
Seibold MA, Smith RW, Urbanek C, et al. The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PloS One 2013;8:e58658.
DOI: https://doi.org/10.1371/journal.pone.0058658
Chen G, Ribeiro CM, Sun L, et al. XBP1S regulates MUC5B in a promoter variant–dependent pathway in idiopathic pulmonary fibrosis airway epithelia. Am J Respir Crit Care Med 2019;200:220-34.
DOI: https://doi.org/10.1164/rccm.201810-1972OC
O'Dwyer DN, Ashley SL, Moore BB. Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 2016;311:L590-601.
DOI: https://doi.org/10.1152/ajplung.00221.2016
Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011;364:1503-12.
DOI: https://doi.org/10.1056/NEJMoa1013660
Raghu G, van den Blink B, Hamblin MJ, et al. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med 2019;7:657-64.
DOI: https://doi.org/10.1016/S2213-2600(19)30172-9
Hewson T, McKeever TM, Gibson JE, et al. Timing of onset of symptoms in people with idiopathic pulmonary fibrosis. Thorax 2017. doi: 10.1136/thoraxjnl-2017-210177.
DOI: https://doi.org/10.1136/thoraxjnl-2017-210177
Cottin V, Hirani NA, Hotchkin DL, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018;27:180076.
DOI: https://doi.org/10.1183/16000617.0076-2018
Putman RK, Gudmundsson G, Araki T, et al. The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes. Eur Respir J 2017;50:1700537.
DOI: https://doi.org/10.1183/13993003.00537-2017
Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest 2009;135:1557-63.
DOI: https://doi.org/10.1378/chest.08-2209
Todd NW, Scheraga RG, Galvin JR, et al. Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis. J Inflamm Res 2013;6:63-70.
DOI: https://doi.org/10.2147/JIR.S40673
Kojima M, Kojima T, Suzuki S, et al. Depression, inflammation, and pain in patients with rheumatoid arthritis. Arthritis Rheum 2009;61:1018-24.
DOI: https://doi.org/10.1002/art.24647
How to Cite
Hassan, Maryam, Akbar Shoukat Ali, Ali Bin Sarwar Zubairi, Zahra Ali Padhani, Salman Kirmani, Huzaifa Ahmad, Zafar Fatmi, and Jai K Das. 2024. “Gene Polymorphisms and Risk of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis”. Monaldi Archives for Chest Disease, October. https://doi.org/10.4081/monaldi.2024.2952.
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