Genetics and Idiopathic Interstitial Pneumonias

Abstract

Significant progress has been made in elucidating the genetics of parenchymal lung diseases, particularly idiopathic interstitial pneumonias (IIPs). IIPs are a heterogeneous group of diffuse interstitial lung diseases of uncertain etiology, diagnosed only after known causes of interstitial lung disease have been excluded. Idiopathic pulmonary fibrosis is the most common IIP. Through candidate gene approaches and genome wide association studies, much light has been shed on the genetic origins of IIPs, enhancing our understanding of risk factors and pathogenesis. However, significant work remains to be accomplished in identifying novel genetic variants and characterizing the function of validated candidate genes in lung pathobiology, their interplay with environmental factors, and ultimately translating these discoveries to patient care.

Keywords

interstitial pneumonia - IPF - surfactant protein - telomere - MUC5B

• References

• 1 Travis WD, Costabel U, Hansell DM , et al; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188 (6) 733-748
• 2 Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006; 174 (7) 810-816
• 3 Wolters PJ, Collard HR, Jones KD. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol 2014; 9: 157-179
• 4 Kropski JA, Lawson WE, Young LR, Blackwell TS. Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Dis Model Mech 2013; 6 (1) 9-17
• 5 García-Sancho C, Buendía-Roldán I, Fernández-Plata MR , et al. Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med 2011; 105 (12) 1902-1907
• 6 Marshall RP, Puddicombe A, Cookson WO, Laurent GJ. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom. Thorax 2000; 55 (2) 143-146
• 7 Lawson WE, Loyd JE. The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?. Proc Am Thorac Soc 2006; 3 (4) 345-349
• 8 Nogee LM, Dunbar III AE, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001; 344 (8) 573-579
• 9 George G, Rosas IO, Cui Y , et al. Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease. Chest 2015; 147 (6) 1549-1557
• 10 Greene KE, King Jr TE, Kuroki Y , et al. Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J 2002; 19 (3) 439-446
• 11 Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 2005; 5 (1) 58-68
• 12 Collard HR, Calfee CS, Wolters PJ , et al. Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2010; 299 (1) L3-L7
• 13 Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol 2004; 66: 601-623
• 14 Thomas AQ, Lane K, Phillips III J , et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002; 165 (9) 1322-1328
• 15 Chibbar R, Shih F, Baga M , et al. Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis. Modern Pathology: an official journal of the United States and Canadian Academy of Pathology. 2004; 17: 973-980
• 16 van Moorsel CH, van Oosterhout MF, 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 (11) 1419-1425
• 17 Ono S, Tanaka T, Ishida M , et al. Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred. Eur Respir J 2011; 38 (4) 861-869
• 18 Lawson WE, Grant SW, Ambrosini V , et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax 2004; 59 (11) 977-980
• 19 Cottin V, Reix P, Khouatra C, Thivolet-Béjui F, Feldmann D, Cordier JF. Combined pulmonary fibrosis and emphysema syndrome associated with familial SFTPC mutation. Thorax 2011; 66 (10) 918-919
• 20 Mulugeta S, Nguyen V, Russo SJ, Muniswamy M, Beers MF. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation. Am J Respir Cell Mol Biol 2005; 32 (6) 521-530
• 21 Maguire JA, Mulugeta S, Beers MF. Endoplasmic reticulum stress induced by surfactant protein C BRICHOS mutants promotes proinflammatory signaling by epithelial cells. Am J Respir Cell Mol Biol 2011; 44 (3) 404-414
• 22 Tanjore H, Cheng DS, Degryse AL , et al. Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress. J Biol Chem 2011; 286 (35) 30972-30980
• 23 Tanjore H, Blackwell TS, Lawson WE. Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012; 302 (8) L721-L729
• 24 Selman M, Lin HM, Montaño M , et al. Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis. Hum Genet 2003; 113 (6) 542-550
• 25 Zhang X, Jiang J, Chen WJ, Su LX, Xie LX. Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis. Chin Med J (Engl) 2012; 125 (11) 1945-1951
• 26 Wang Y, Kuan PJ, Xing C , et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet 2009; 84 (1) 52-59
• 27 Maitra M, Wang Y, Gerard RD, Mendelson CR, Garcia CK. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress. J Biol Chem 2010; 285 (29) 22103-22113
• 28 Vázquez de Lara L, Becerril C, Montaño M , et al. Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression. Am J Physiol Lung Cell Mol Physiol 2000; 279 (5) L950-L957
• 29 Wert SE, Whitsett JA, Nogee LM. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 2009; 12 (4) 253-274
• 30 Campo I, Zorzetto M, Mariani F , et al. A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant. Respir Res 2014; 15: 43
• 31 Coghlan MA, Shifren A, Huang HJ , et al. Sequencing of idiopathic pulmonary fibrosis-related genes reveals independent single gene associations. BMJ Open Respir Res 2014; 1 (1) e000057
• 32 Young LR, Nogee LM, Barnett B, Panos RJ, Colby TV, Deutsch GH. Usual interstitial pneumonia in an adolescent with ABCA3 mutations. Chest 2008; 134 (1) 192-195
• 33 Bullard JE, Nogee LM. Heterozygosity for ABCA3 mutations modifies the severity of lung disease associated with a surfactant protein C gene (SFTPC) mutation. Pediatr Res 2007; 62 (2) 176-179
• 34 Fingerlin TE, Murphy E, Zhang W , et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013; 45 (6) 613-620
• 35 López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153 (6) 1194-1217
• 36 Shammas MA. Telomeres, lifestyle, cancer, and aging. Curr Opin Clin Nutr Metab Care 2011; 14 (1) 28-34
• 37 Kirwan M, Dokal I. Dyskeratosis congenita: a genetic disorder of many faces. Clin Genet 2008; 73 (2) 103-112
• 38 Armanios M. Telomerase and idiopathic pulmonary fibrosis. Mutat Res 2012; 730 (1–2) 52-58
• 39 Armanios MY, Chen JJ, Cogan JD , et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 2007; 356 (13) 1317-1326
• 40 Tsakiri KD, Cronkhite JT, Kuan PJ , et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A 2007; 104 (18) 7552-7557
• 41 Mushiroda T, Wattanapokayakit S, Takahashi A , et al; Pirfenidone Clinical Study Group. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet 2008; 45 (10) 654-656
• 42 Cogan JD, Kropski JA, Zhao M , et al. Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med 2015; 191 (6) 646-655
• 43 Stuart BD, Choi J, Zaidi S , et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet 2015; 47 (5) 512-517
• 44 Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am J Hum Genet 2013; 92 (3) 448-453
• 45 Deng Z, Glousker G, Molczan A , et al. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome. Proc Natl Acad Sci U S A 2013; 110 (36) E3408-E3416
• 46 Kannengiesser C, Borie R, Ménard C , et al. Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis. Eur Respir J 2015; 46 (2) 474-485
• 47 Tummala H, Walne A, Collopy L , et al. Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita. J Clin Invest 2015; 125 (5) 2151-2160
• 48 Heiss NS, Knight SW, Vulliamy TJ , et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 1998; 19 (1) 32-38
• 49 Alder JK, Parry EM, Yegnasubramanian S , et al. Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene. Hum Mutat 2013; 34 (11) 1481-1485
• 50 Kropski JA, Mitchell DB, Markin C , et al. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest 2014; 146 (1) e1-e7
• 51 Hisata S, Sakaguchi H, Kanegane H , et al. A novel missense mutation of DKC1 in dyskeratosis congenita with pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2013; 30 (3) 221-225
• 52 Safa WF, Lestringant GG, Frossard PM. X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation. Thorax 2001; 56 (11) 891-894
• 53 Frank AK, Tran DC, Qu RW, Stohr BA, Segal DJ, Xu L. The shelterin TIN2 subunit mediates recruitment of telomerase to telomeres. PLoS Genet 2015; 11 (7) e1005410
• 54 Fukuhara A, Tanino Y, Ishii T , et al. Pulmonary fibrosis in dyskeratosis congenita with TINF2 gene mutation. Eur Respir J 2013; 42 (6) 1757-1759
• 55 Alder JK, Stanley SE, Wagner CL, Hamilton M, Hanumanthu VS, Armanios M. Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis. Chest 2015; 147 (5) 1361-1368
• 56 Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008; 112 (9) 3594-3600
• 57 Levy D, Neuhausen SL, Hunt SC , et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc Natl Acad Sci U S A 2010; 107 (20) 9293-9298
• 58 Codd V, Nelson CP, Albrecht E , et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 2013; 45 (4) 422-427 , e1–e2
• 59 Wan M, Qin J, Songyang Z, Liu D. OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J Biol Chem 2009; 284 (39) 26725-26731
• 60 Cronkhite JT, Xing C, Raghu G , et al. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med 2008; 178 (7) 729-737
• 61 Müezzinler A, Mons U, Dieffenbach AK , et al. Smoking habits and leukocyte telomere length dynamics among older adults: results from the ESTHER cohort. Exp Gerontol 2015; 70: 18-25
• 62 Raschenberger J, Kollerits B, Ritchie J , et al. Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes. Sci Rep 2015; 5: 11887
• 63 Arish N, Cohen PY, Golan-Gerstl R , et al. Overexpression of telomerase protects human and murine lung epithelial cells from Fas- and bleomycin-induced apoptosis via FLIP upregulation. PLoS ONE 2015; 10 (5) e0126730
• 64 Degryse AL, Xu XC, Newman JL , et al. Telomerase deficiency does not alter bleomycin-induced fibrosis in mice. Exp Lung Res 2012; 38 (3) 124-134
• 65 Celli GB, de Lange T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 2005; 7 (7) 712-718
• 66 Alder JK, Barkauskas CE, Limjunyawong N , et al. Telomere dysfunction causes alveolar stem cell failure. Proc Natl Acad Sci U S A 2015; 112 (16) 5099-5104
• 67 Seibold MA, Wise AL, Speer MC , et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364 (16) 1503-1512
• 68 Ensembl Project. http://useast.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=11:1240721-1241721;v=rs35705950;vdb=variation;vf=10259152 . Accessed March 9, 2016
• 69 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 (16) 1576-1577
• 70 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 (5) 436-441
• 71 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 (8) e70621
• 72 Horimasu Y, Ohshimo S, Bonella F , et al. MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology 2015; 20 (3) 439-444
• 73 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 (2) 460-464
• 74 Ji X, Wu B, Jin K , et al. MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a Chinese population. Mol Biol Rep 2014; 41 (7) 4171-4176
• 75 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 (6) 463-470
• 76 Peljto AL, Zhang Y, Fingerlin TE , et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 2013; 309 (21) 2232-2239
• 77 Cosgrove GP, Groshong S, Peljto AL , et al. The MUC5B Promoter Polymorphism Is Associated with a Less Severe Pathological Form of Familial Interstitial Pneumonia (FIP). San Francisco, CA: American Thoracic Society International Conference; 2012
• 78 Doyle TJ, Hunninghake GM, Rosas IO. Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med 2012; 185 (11) 1147-1153
• 79 Hunninghake GM, Hatabu H, Okajima Y , et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 2013; 368 (23) 2192-2200
• 80 Chen Y, Zhao YH, Di YP, Wu R. Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5′-flanking region. Am J Respir Cell Mol Biol 2001; 25 (5) 542-553
• 81 Casalino-Matsuda SM, Monzon ME, Day AJ, Forteza RM. Hyaluronan fragments/CD44 mediate oxidative stress-induced MUC5B up-regulation in airway epithelium. Am J Respir Cell Mol Biol 2009; 40 (3) 277-285
• 82 Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 2006; 86 (1) 245-278
• 83 Zhen G, Park SW, Nguyenvu LT , et al. IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production. Am J Respir Cell Mol Biol 2007; 36 (2) 244-253
• 84 Roy MG, Livraghi-Butrico A, Fletcher AA , et al. Muc5b is required for airway defence. Nature 2014; 505 (7483) 412-416
• 85 Molyneaux PL, Cox MJ, Willis-Owen SA , et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2014; 190 (8) 906-913
• 86 Liptzin DR, Watson AM, Murphy E , et al. MUC5B expression and location in surfactant protein C mutations in children. Pediatr Pulmonol 2015;
• 87 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 (4) 309-317
• 88 Zhu L, Wang L, Luo X , et al. Tollip, an intracellular trafficking protein, is a novel modulator of the transforming growth factor-β signaling pathway. J Biol Chem 2012; 287 (47) 39653-39663
• 89 Naik PK, Moore BB. Viral infection and aging as cofactors for the development of pulmonary fibrosis. Expert Rev Respir Med 2010; 4 (6) 759-771
• 90 Vannella KM, Luckhardt TR, Wilke CA, van Dyk LF, Toews GB, Moore BB. Latent herpesvirus infection augments experimental pulmonary fibrosis. Am J Respir Crit Care Med 2010; 181 (5) 465-477
• 91 Pulkkinen V, Bruce S, Rintahaka J , et al. ELMOD2, a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses. FASEB J 2010; 24 (4) 1167-1177
• 92 O'Dwyer DN, Armstrong ME, Trujillo G , et al. The toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2013; 188 (12) 1442-1450
• 93 Hodgson U, Pulkkinen V, Dixon M , et al. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis. Am J Hum Genet 2006; 79 (1) 149-154
• 94 Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J. Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest 2001; 107 (12) 1529-1536
• 95 Whyte M, Hubbard R, Meliconi R , et al. Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms. Am J Respir Crit Care Med 2000; 162 (2, Pt 1) 755-758
• 96 Riha RL, Yang IA, Rabnott GC, Tunnicliffe AM, Fong KM, Zimmerman PV. Cytokine gene polymorphisms in idiopathic pulmonary fibrosis. Intern Med J 2004; 34 (3) 126-129
• 97 Barlo NP, van Moorsel CH, Korthagen NM , et al. Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis. Clin Exp Immunol 2011; 166 (3) 346-351
• 98 Pantelidis P, Fanning GC, Wells AU, Welsh KI, Du Bois RM. Analysis of tumor necrosis factor-alpha, lymphotoxin-alpha, tumor necrosis factor receptor II, and interleukin-6 polymorphisms in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001; 163 (6) 1432-1436
• 99 Louis E, Franchimont D, Piron A , et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 1998; 113 (3) 401-406
• 100 Vasakova M, Striz I, Slavcev A , et al. Correlation of IL-1alpha and IL-4 gene polymorphisms and clinical parameters in idiopathic pulmonary fibrosis. Scand J Immunol 2007; 65 (3) 265-270
• 101 Vasakova M, Striz I, Slavcev A, Jandova S, Kolesar L, Sulc J. Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis. Tissue Antigens 2006; 67 (3) 229-232
• 102 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
• 103 Latsi P, Pantelidis P, Vassilakis D, Sato H, Welsh KI, du Bois RM. Analysis of IL-12 p40 subunit gene and IFN-gamma G5644A polymorphisms in idiopathic pulmonary fibrosis. Respir Res 2003; 4: 6
• 104 Xaubet A, Fu WJ, Li M , et al. A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2010; 27 (2) 121-130
• 105 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 (3) 330-334
• 106 Bournazos S, Bournazou I, Murchison JT , et al. Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis. Respiration 2011; 81 (2) 142-149
• 107 Bournazos S, Grinfeld J, Alexander KM , et al. Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression. BMC Pulm Med 2010; 10: 51
• 108 Bournazos S, Bournazou I, Murchison JT , et al. Fcγ receptor IIIb (CD16b) polymorphisms are associated with susceptibility to idiopathic pulmonary fibrosis. Lung 2010; 188 (6) 475-481
• 109 Korthagen NM, van Moorsel CH, Barlo NP, Kazemier KM, Ruven HJ, Grutters JC. Association between variations in cell cycle genes and idiopathic pulmonary fibrosis. PLoS ONE 2012; 7 (1) e30442
• 110 Xue J, Gochuico BR, Alawad AS , et al. The HLA class II Allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis. PLoS ONE 2011; 6 (2) e14715
• 111 Falfán-Valencia R, Camarena A, Juárez A , et al. Major histocompatibility complex and alveolar epithelial apoptosis in idiopathic pulmonary fibrosis. Hum Genet 2005; 118 (2) 235-244
• 112 Li XX, Li N, Ban CJ, Zhu M, Xiao B, Dai HP. Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-β1 and plasminogen activator inhibitor 1. Chin Med J (Engl) 2011; 124 (13) 1923-1927
• 113 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 (2) 199-205
• 114 Kim KK, Flaherty KR, Long Q , et al. A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. Mol Med 2003; 9 (1-2) 52-56
• 115 Pardo A, Selman M. Role of matrix metaloproteases in idiopathic pulmonary fibrosis. Fibrogenesis Tissue Repair 2012; 5 (Suppl. 01) S9
• 116 Zuo F, Kaminski N, Eugui E , et al. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci U S A 2002; 99 (9) 6292-6297
• 117 Pardo A, Selman M, Kaminski N. Approaching the degradome in idiopathic pulmonary fibrosis. Int J Biochem Cell Biol 2008; 40 (6-7) 1141-1155
• 118 Rosas IO, Richards TJ, Konishi K , et al. MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 2008; 5 (4) e93
• 119 Richards TJ, Park C, Chen Y , et al. Allele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012; 302 (8) L746-L754
• 120 Checa M, Ruiz V, Montaño M, Velázquez-Cruz R, Selman M, Pardo A. MMP-1 polymorphisms and the risk of idiopathic pulmonary fibrosis. Hum Genet 2008; 124 (5) 465-472
• 121 Wyatt CA, Coon CI, Gibson JJ, Brinckerhoff CE. Potential for the 2G single nucleotide polymorphism in the promoter of matrix metalloproteinase to enhance gene expression in normal stromal cells. Cancer Res 2002; 62 (24) 7200-7202
• 122 King Jr TE, Bradford WZ, Castro-Bernardini S , et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014; 370 (22) 2083-2092
• 123 Richeldi L, du Bois RM, Raghu G , et al; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014; 370 (22) 2071-2082
• 124 El-Chemaly S, Ziegler SG, Calado RT , et al. Natural history of pulmonary fibrosis in two subjects with the same telomerase mutation. Chest 2011; 139 (5) 1203-1209
• 125 Garcia CK. Running short on time: lung transplant evaluation for telomere-related pulmonary fibrosis. Chest 2015; 147 (6) 1450-1452
• 126 Tokman S, Singer JP, Devine MS , et al. Clinical outcomes of lung transplant recipients with telomerase mutations. J Heart Lung Transplant 2015; 34 (10) 1318-1324
• 127 Silhan LL, Shah PD, Chambers DC , et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J 2014; 44 (1) 178-187