Revisión en profundidad: genética, fisiopatología, clínica | 26 MAY 14

Determinantes genéticos de la fibrosis pulmonar

Los estudios genéticos ofrecen la esperanza de identificar con más precisión a los individuos en riesgo de fibrosis pulmonar idiopática; de definir la patogenia de la enfermedad y de crear futuros tratamientos dirigidos
Autor/a: Dres. Spagnolo P, Grunewald J, du Bois RM Lancet Respir Med 2014
INDICE:  1.  | 2. 

1 Eckes B, Kessler D, Aumailley M, Krieg T. Interactions of fibroblasts with the extracellular matrix: implications for the understanding of fi brosis. Springer Semin Immunopathol 2000; 21: 415–29.
2 Wynn TA. Cellular and molecular mechanisms of fi brosis. J Pathol 2008; 214: 199–210.
3 Macneal K, Schwartz DA. The genetic and environmental causes of pulmonary fi brosis. Proc Am Thorac Soc 2012; 9: 120–25.
4 Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classifi cation of the idiopathic interstitial pneumonias.
5 Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fi brosis. Am J Respir Crit Care Med 1998; 157: 199–203.
6 Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fi brosis. Am J Respir Crit Care Med 2011; 183: 431–40.
7 Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fi brosis (CAPACITY): two randomized trials. Lancet 2011; 377: 1760–69.
8 Richeldi L, Costabel U, Selman M, et al. Effi cacy of a tyrosine kinase inhibitor in idiopathic pulmonary fi brosis. N Engl J Med 2011; 365: 1079–87.
9 Spagnolo P, Luppi F, Cerri S, Richeldi L. Genetic testing in diffuse parenchymal lung disease. Orphanet J Rare Dis 2012; 7: 79.
10 Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fi brosis. N Engl J Med 2007; 356: 1317–26.
11 Depinho RA, Kaplan KL. The Hermansky-Pudlak syndrome: report of three cases and review of pathophysiology and management considerations. Medicine 1985; 64: 192–202.
12 Javaheri S, Lederer DH, Pella JA, Mark GJ, Levine BW. Idiopathic pulmonary fibrosis in monozygotic twins: the importance of genetic predisposition. Chest 1980; 78:  591–94.
13 Hughes EW. Familial interstitial pulmonary fi brosis. Thorax 1964; 19: 515–25.
14 Bitterman PB, Rennard SI, Keogh BA, Wewers MD, Adelberg S, Crystal RG. Familial idiopathic pulmonary fibrosis: evidence of lung inflammation in unaffected members. N Engl J Med 1986; 314: 1343–47.
15 Steele MP, Speer MC, Loyd JE, et al. Clinical and pathological features of familial interstitial pneumonia. Am J Respir Crit Care Med 2005; 172: 1146–52.
16 Hodgson U, Laitinen T, Tukiainen P. Nationwide prevalence of sporadic and familial idiopathic pulmonary fi brosis: evidence of founder effect among multiplex families in Finland. Thorax 2002; 57: 338–42.
17 Peabody JW, Peabody JW Jr, Hayes EW, et al. Idiopathic pulmonary fibrosis; its occurrence in identical twin sisters. Dis Chest 1950; 18: 330–44.
18 MacMillan JM. Familial pulmonary fi brosis. Dis Chest 1951; 20: 426–36.
19 van Moorsel CH, van Oosterhout MF, Barlo NP, et al. SFTPC 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.
20 Lawson WE, Loyd JE, Degryse AL. Genetics in pulmonary fi brosis—familial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis. Am J Med Sci 2011; 341: 439–43.
21 Lee H, Ryu JH, Wittmer MH, et al. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Chest 2005; 127: 2034–41.
22 Marshall RP, Puddicombe A, Cookson WO, et al. Adult familial cryptogenic fi brosing alveolitis in the United Kingdom. Thorax 2000; 55: 143–46.
23 Lee HY, Seo JB, Steele MP, et al. High-resolution CT scan findings in familial interstitial pneumonia do not conform to those of idiopathic interstitial pneumonia. Chest 2012; 142: 1577–83.
24 Nogee LM, Dunbar AE 3rd, 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: 573–79.
25 Thomas AQ, Lane K, Phillips J 3rd, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecifi c interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002; 165: 1322–28.
26 Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med 2002; 347: 2141–48.
27 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: 521–30.
28 Lawson WE, Crossno PF, Polosukhin VV, et al. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am J Physiol Lung Cell Mol Physiol 2008;
294: L1119–26.
29 Korfei M, Ruppert C, Mahavadi P, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008; 178: 838–46.
30 Wang Y, Kuan PJ, Xing C, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fi brosis and lung cancer. Am J Hum Genet 2009; 84: 52–59.
31 Maitra M, Wang Y, Gerard RD, Mendelson CR, Garcia CK. Surfactant protein A2 mutations associated with pulmonary fi brosis lead to protein instability and endoplasmic reticulum stress. J Biol Chem 2010; 285: 22103–13.
32 Calado RT, Young NS. Telomere diseases. N Engl J Med 2009; 361: 2353–65.
33 Nelson ND, Bertuch AA. Dyskeratosis congenita as a disorder of telomere maintenance. Mutat Res 2012; 730: 43–51.
34 Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000; 110: 768–79.
35 Vulliamy T, Marrone A, Szydlo R, et al. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 2004; 36: 447–49.
36 Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001; 413: 432–35.
37 Armanios M, Chen JL, Chang YP, et al. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci USA 2005; 102: 15960–64.
38 Vulliamy T, Dokal I. Dyskeratosis congenita. Semin Hematol 2006; 43: 157–66.
39 Tsakiri KD, Cronkhite JT, Kuan PJ, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA 2007; 104: 7552–57.
40 Cronkhite JT, Xing C, Raghu G, et al. Telomere shortening in familial and sporadic pulmonary fi brosis. Am J Respir Crit Care Med 2008; 178: 729–37.
41 Alder JK, Chen JJ, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fi brosis. Proc Natl Acad Sci USA 2008; 105: 13051–56.
42 Armanios M. Telomerase and idiopathic pulmonary fibrosis. Mutat Res 2012; 730: 52–58.
43 Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence in patients with pulmonary emphysema. Am J Respir Crit Care Med 2006; 174: 886–93.
44 Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking, and telomere length in women. Lancet 2005; 366: 662–64.
45 O’Sullivan JN, Bronner MP, Brentnall TA, et al. Chromosomal instability in ulcerative colitis is related to telomere shortening. Nat Genet 2002; 32: 280–84.
46 Risques RA, Lai LA, Brentnall TA, et al. Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage. Gastroenterology 2008; 135: 410–18.
47 Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet 2009; 10: 45–61.
48 Gribbin J, Hubbard R, Smith C. Role of diabetes mellitus and gastro-oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Respir Med 2009; 103: 927–31.
49 International HapMap Consortium. A haplomap type of the human genome. Nature 2005; 437: 1299–320.
50 Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet 2005; 6: 109–18.
51 Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010; 363: 166–76.
52 Hodgson U, Pulkkinen V, Dixon M, et al. ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis. Am J Hum Genet 2006; 79: 149–54.
53 Pulkkinen V, Bruce S, Rintahaka J, et al. ELMOD2, a candidate gene for idiopathic pulmonary fi brosis, regulates antiviral responses. FASEB J 2010; 24: 1167–77.
54 Mushiroda T, Wattanapokayakit S, Takahashi A, et al. A genomewide association study identifi es an association of a common variant in TERT with susceptibility to idiopathic pulmonary fi brosis. J Med Genet 2008; 45: 654–56. 12
55 Korthagen NM, van Moorsel CH, Barlo NP, Kazemier KM, Ruven HJ, Grutters JC. Association between variations in cell cycle genes and idiopathic pulmonary fi brosis. PLoS One 2012; 7: e30442
56 Xue J, Gochuico BR, Alawad AS, et al. The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fi brosis. PLoS One 2011; 6: e14715.
57 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: 755–58.
58 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 fi brosis. Clin Exp Immunol 2011; 166: 346–51.
59 Korthagen NM, van Moorsel CH, Kazemier KM, Ruven HJ, Grutters JC. IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study. Immunogenetics 2012; 64: 371–77.
60 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 fi brosis via the IL-8 protein enhancing mode. Respir Res 2011; 12: 73.
61 Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fi brosis. N Engl J Med 2011; 364: 1503–12.
62 Zhang Y, Noth I, Garcia GN, Kaminski N. A variant in the promoter of MUC5B and idiopathic pulmonary fi brosis. N Engl J Med 2011; 364: 1576–77.
63 Stock CJ, Sato H, Fonseca C, et al. Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fi brosis but not with development of lung fi brosis in systemic sclerosis or sarcoidosis. Thorax 2013; 68: 436–41.
64 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: 2232–39.
65 Xaubet A, Marin-Arguedas A, Lario S, et al. Transforming growth factor-b1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fi brosis. Am J Respir Crit Care Med 2003; 168: 431–35.
66 Son JY, Kim SY, Cho SH, et al. TGF-β1 T869C polymorphism may affect susceptibility to idiopathic pulmonary fi brosis and disease severity. Lung 2013; 191: 199–205.
67 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.
68 Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fi brosis. Nat Genet 2013; 45: 613–20.
69 Nekrasova O, Green KJ. Desmosome assembly and dynamics. Trends Cell Biol 2013; 23: 537–46.
70 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.
71 Peljto AL, Steele MP, Fingerlin TE, et al. The pulmonary fibrosis associated
MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis. Chest 2012; 142: 1584–88.
72 Odoardi F, Sie C, Streyl K, et al. T cells become licensed in the lung to enter the central nervous system. Nature 2012; 488: 675–79.
73 Fischer A, du Bois RM. Interstitial lung disease in connective tissue disorders. Lancet 2012; 380: 689–98.
74 Park JH, Kim DS, Park IN, et al. Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med 2007; 175: 705–11.
75 Nalysnyk L, Cid-Ruzafa J, Rotella P, Essere D. Incidence and prevalence of idiopathic pulmonary fi brosis: review of the literature. Eur Respir Rev 2012; 21: 355–61.
76 Klareskog L, Stolt P, Lundberg K, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modifi ed by citrullination. Arthritis Rheum 2006; 54: 38–46.
77 Makrygiannakis D, Hermansson M, Ulfgren AK, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis 2008; 67: 1488–92.
78 Reynisdottir G, Karimi R, Joshua V, et al. Structural lung changes and local anti-citrulline immunity are early features of anti citrullinated proteins antibodies positive rheumatoid arthritis. Arthritis Rheum 2013; published online Oct 21. DOI:10.1002/art.38201.
79 Rantapaa-Dahlqvist S, de Jong BA, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 2003; 48: 2741–49.
80 Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009; 373: 659–72.
81 Kim EJ, Collard HR, King TE Jr. Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern. Chest 2009; 136: 1397–405.
82 Mori S, Cho I, Koga Y, Sugimoto M. Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis. J Rheumatol 2008; 35: 1513–21.
83 Turesson C. Extra-articular rheumatoid arthritis. Curr Opin Rheumatol 2013; 25: 360–66.
84 Charles PJ, Sweatman MC, Markwick JR, Maini RN. HLA-B40: a marker for susceptibility to lung disease in rheumatoid arthritis. Dis Markers 1991; 9: 97–101.
85 Sugiyama Y, Ohno S, Kano S, Maeda H, Kitamura S. Diffuse panbronchiolitis and rheumatoid arthritis: a possible correlation with HLA-B54. Intern Med 1994; 33: 612–14.
86 Scott TE, Wise RA, Hochberg MC, Wigley FM. HLA-DR4 and pulmonary dysfunction in rheumatoid arthritis. Am J Med 1987; 82: 765–71.
87 Migita K, Nakamura T, Koga T, Eguchi K. HLA-DRB1 alleles and rheumatoid arthritis-related pulmonary fibrosis. J Rheumatol 2010; 37: 205–07.
88 Furukawa H, Oka S, Shimada K, et al. Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope. PLoS One 2012; 7: e33133.
89 Fischer A, Solomon JJ, du Bois RM, et al. Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease. Respir Med 2012; 106; 1040–47.
90 Sharif R, Mayes MD, Tan FK, et al. IRF5 polymorphism predicts prognosis in patients with systemic sclerosis. Ann Rheum Dis 2012; 71: 1197–202.
91 Assassi S, Del Junco D, Sutter K, et al. Clinical and genetic factors predictive of mortality in early systemic sclerosis. Arthritis Rheum 2009; 61: 1403–11.
92 Goh NS, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008; 177: 1248–54.
93 Steen VD, Powell DL, Medsger TA Jr. Clinical correlations and prognosis based on serum autoantibodies in patients with progressive systemic sclerosis. Arthritis Rheum 1988; 31: 196–203.
94 Vlachoyiannopoulos PG, Dafni UG, Pakas I, Spyropoulou-Vlachou M, Stavropoulos-Giokas C, Moutsopoulos HM. Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele. Ann Rheum Dis 2000; 59: 359–67.
95 Gilchrist FC, Bunn C, Foley PJ, et al. Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP. Genes Immun 2001; 2: 76–81.
96 Tikly M, Rands A, McHugh N, Wordsworth P, Welsh K. Human leukocyte antigen class II associations with systemic sclerosis in South Africans. Tissue Antigens 2004; 63: 487–90.
97 Radstake TR, Gorlova O, Rueda B, et al. Genome-wide association study of systemic sclerosis identifi es CD247 as a new susceptibility locus. Nat Genet 2010; 42: 426–29.
98 Black CM, Silman AJ, Herrick AI, et al. Interferon-alpha does not improve outcome at one year in patients with diff use cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1999; 42: 299–305.
99 Koumakis E, Bouaziz M, Dieude P, et al. A regulatory variant in CCR6 is associated with anti-topoisomerase positive systemic sclerosis susceptibility. Arthritis Rheum 2013; 65: 3202–08.
100 Dieude P, Guedj M, Wipff J, et al. NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis. Ann Rheum Dis 2011; 70: 668–74.
101 Abehsera M, Valeyre D, Grenier P, Jaillet H, Battesti JP, Brauner MW. Sarcoidosis with pulmonary fibrosis: CT patterns and correlation with pulmonary function. AJR Am J Roentgenol 2000; 174: 1751–57.
102 Rybicki BA, Iannuzzi MC, Frederick MM, et al. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med 2001; 164: 2085–91.
103 Sverrild A, Backer V, Kyvik KO, et al, Heredity in sarcoidosis: a registry-based twin study. Thorax 2008; 63: 894–96.
104 Judson M, Hirst K, Ivengar SK, et al. Comparison of sarcoidosis phenotypes among aff ected African-American siblings. Chest 2006; 130: 855–62.
105 Spagnolo P, Grunewald J. Recent advances in the genetics of sarcoidosis. J Med Genet 2013; 50: 290–97.
106 Grunewald J, Eklund A. Lofgren’s syndrome: human leukocyte antigen strongly infl uences the disease course. Am J Respir Crit Care Med 2009; 179: 307–12.
107 Li Y, Wollnik B, Pabst S, et al. BTNL2 gene variant and sarcoidosis. Thorax 2006; 61: 273–74.
108 Wijnen PA, Voorter CE, Nelemans PJ, Verschakelen JA, Bekers O, Drent M. Butyrophilin-like 2 in pulmonary sarcoidosis: a factor for susceptibility and progression? Hum Immunol 2011; 72: 342–47.
109 Spagnolo P, Sato H, Grutters JC, et al. Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis. Tissue Antigens 2007; 70: 219–27.
110 Heron M, van Moorsel CH, Grutters JC, et al. Genetic variation in GREM1 is a risk factor for fi brosis in pulmonary sarcoidosis. Tissue Antigens 2010; 77: 112–17.
111 Sato H, Williams HR, Spagnolo P, et al. CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis. Eur Respir J 2010; 35: 324–30.
112 Kruit A, Grutters JC, Ruven HJ, et al. Transforming growth factor-beta gene polymorphisms in sarcoidosis patients with and without fi brosis. Chest 2006; 129: 1584–91.
113 Lawson WE, Polosukhin VV, Stathopoulos GT, et al. Increased and prolonged pulmonary fi brosis in surfactant protein C–defi cient mice following intratracheal bleomycin. Am J Pathol 2005; 167: 1267–77.
114 Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest 2012; 122: 2756–62.
115 Parker D, Prince A. Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol 2011; 45: 189–201.
116 Plantier L, Crestani B, Wert SE, et al. Ectopic respiratory epithelial cell differentiation in bronchiolised distal airspaces in idiopathic pulmonary fi brosis. Thorax 2011; 66: 651–57.
117 Seibold MA, Smith RW, Urbanek C, et al. The idiopathic pulmonary fi brosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS One 2013; 8: e58658.
118 Boucher RC. Idiopathic pulmonary fibrosis—a sticky business. N Engl J Med 2011; 364: 1560–61.
119 Martino MB, Jones L, Brighton B, et al. The ER stress transducer IRE1β is required for airway epithelial mucin production. Mucosal Immunol 2013; 6: 639–54.
120 Vuga LJ, Ben-Yehudah A, Kovkarova-Naumovski E, et al. WNT5A is a regulator of fi broblast proliferation and resistance to apoptosis. Am J Respir Cell Mol Biol 2009; 41: 583–89.
121 Gunther A, Korfei M, Mahavadi P, von der Beck D, Ruppert C, Markart P. Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis. Eur Respir Rev 2012; 21: 152–60.
122 Wynn TA. Integrating mechanisms of pulmonary fibrosis. J Exp Med 2011; 208: 1339–50.
123 Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 2003; 200: 500–03.
124 Wells AU, Cullinan P, Hansell DM, et al. Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 1994; 149: 1583–90.
125 Koli K, Myllarniemi M, Vuorinen K, et al. Bone morphogenetic protein-4 inhibitor gremlin is overexpressed in idiopathic pulmonary fibrosis. Am J Pathol 2006; 169: 61–71.
126 Raghu G, Anstrom KJ, King TE Jr, et al, for the Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine and N-acetylcysteine for pulmonary fi brosis. N Engl J Med 2012; 366: 1968–77.
127 Maher TM. Idiopathic pulmonary fibrosis: pathobiology of novel approaches to treatment. Clin Chest Med 2012; 33: 69–83.
128 Herazo-Maya JD, Noth I, Duncan SR, et al. Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med 2013; 5: 205ra136.
129 Yang IV, Coldren CD, Leach SM, et al. Expression of cilium-associated genes defi nes novel molecular subtypes of idiopathic pulmonary fi brosis. Thorax 2013; 68: 1114–21.
130 van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profi ling predicts clinical outcome of breast cancer. Nature 2002; 415: 530–36.
131 Chen HY, Yu SL, Chen CH, et al. A fi ve-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 2007; 356: 11–20.
132 Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature 2009; 461: 747–53.
133 Yang IV, Schwartz DA. The next-generation of complex lung genetic studies. Am J Respir Crit Care Med 2012; 186: 1087–94.
134 Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457–63.
135 Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004; 4: 143–53.
136 Yang IV. Epigenomics of idiopathic pulmonary fi brosis. Epigenomics 2012; 4: 195–203.
137 Dakhlallah D, Batte K, Wang Y, et al. Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fi brosis. Am J Respir Crit Care Med 2013; 187: 397–405.
138 Sanders YY, Ambalavanan N, Halloran B, et al. Altered DNA methylation profi le in idiopathic pulmonary fibrosis. Am J Respir Crit Car e Med 2012; 186: 525–35.
 

 

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