Genetic testing in diffuse parenchymal lung disease

Orphanet Journal of Rare Diseases

Volumn 7, Issue 1, 2012, Pages

  Spagnolo, Paolo ^a   Luppi, Fabrizio ^a   Cerri, Stefania ^a   Richeldi, Luca ^a  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

Diffuse parenchymal lung disease; Genetics; Idiopathic pulmonary fibrosis; Sarcoidosis

Indexed keywords

DYSKERIN; ESTRONE; MUCIN 5AC; MUCIN 5B; SURFACTANT PROTEIN C; TELOMERASE; TUBERIN;

BIRT HOGG DUBE SYNDROME; DIFFUSE PARENCHYMAL LUNG DISEASE; DISEASE PREDISPOSITION; DYSKERATOSIS CONGENITA; ENVIRONMENTAL FACTOR; FIBROSING ALVEOLITIS; GENE INTERACTION; GENE MUTATION; GENETIC DISORDER; GENETIC PREDISPOSITION; GENETIC SCREENING; HUMAN; LUNG DISEASE; LUNG FIBROSIS; LUNG SARCOIDOSIS; LYMPHANGIOLEIOMYOMATOSIS; OCULAR ALBINISM; PATHOGENESIS; PHENOTYPE; REVIEW; SILICOSIS; SMOKING; TUBEROUS SCLEROSIS; VASCULAR DISEASE;

GENETIC TESTING; HUMANS; LUNG DISEASES;

EID: 84867437029     PISSN: None     EISSN: 17501172     Source Type: Journal    
DOI: 10.1186/1750-1172-7-79     Document Type: Review

References (72)

1. Cellular and molecular mechanisms of fibrosis. Wynn TA, J Pathol 2008 214 199 210 10.1002/path.2277 18161745 (Pubitemid 351160157)
2. Genetic predisposition to respiratory diseases: infiltrative lung diseases. Steele MP, Brown KK, Respiration 2007 74 601 608 10.1159/000110204 18037811 (Pubitemid 350164503)
3. Clinical and pathological features of familial interstitial pneumonia. Steele MP, Speer MC, Loyd JE, Brown KK, Herron A, Slifer SH, Burch LH, Wahidi MM, Phillips JA, Sporn TA, McAdams HP, Schwarz MI, Schwartz DA, Am J Respir Crit Care Med 2005 172 1146 1152 10.1164/rccm.200408-1104OC 16109978 (Pubitemid 43066651)
4. Early interstitial lung disease in familial pulmonary fibrosis. Rosas IO, Ren P, Avila NA, Chow CK, Franks TJ, Travis WD, McCoy JP, May RM, Wu HP, Nguyen DM, Arcos-Burgos M, MacDonald SD, Gochuico BR, Am J Respir Crit Care Med 2007 176 698 7055 10.1164/rccm.200702-254OC 17641157 (Pubitemid 47503078)
5. An Official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Raghu G, Collard HR, Egan JJ, et al. Am J Respir Crit Care Med 2011 183 788 824 10.1164/rccm.2009- 040GL 21471066
6. Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland. Hodgson U, Laitinen T, Tukiainen P, Thorax 2002 57 338 342 10.1136/thorax.57.4. 338 11923553 (Pubitemid 34298932)
7. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Lee H, Ryu JH, Wittmer MH, Hartman TE, Lymp JF, Tazelaar HD, Limper AH, Chest 2005 127 2034 2041 10.1378/chest.127.6.2034 15947317
8. Gene expression profiling of familial and sporadic interstitial pneumonia. Yang IV, Burch LH, Steele MP, Savov JD, Hollingsworth JW, McElvania-Tekippe E, Berman KG, Speer MC, Sporn TA, Brown KK, Schwarz MI, Schwartz DA, Am J Respir Crit Care Med 2007 175 45 54 16998095 (Pubitemid 46105308)
9. Hydrophobic surfactant proteins in lung function and disease. Whitsett JA, Weaver TE, N Engl J Med 2002 347 2141 2148 10.1056/NEJMra022387 12501227 (Pubitemid 36015127)
10. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation. Mulugeta S, Nguyen V, Russo SJ, Muniswamy M, Beers MF, Am J Respir Cell Mol Biol 2005 32 521 530 10.1165/rcmb.2005-0009OC 15778495 (Pubitemid 40770130)
11. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Lawson WE, Crossno PF, Polosukhin VV, Roldan J, Cheng DS, Lane KB, Blackwell TR, Xu C, Markin C, Ware LB, Miller GG, Loyd JE, Blackwell TS, Am J Physiol Lung Cell Mol Physiol 2008 294 1119 L1126 10.1152/ajplung.00382.2007 18390830
12. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M, Lang G, Fink L, Bohle RM, Seeger W, Weaver TE, Guenther A, Am J Respir Crit Care Med 2008 178 838 846 10.1164/rccm.200802-313OC 18635891
13. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK, Am J Hum Genet 2009 84 52 59 10.1016/j.ajhg.2008.11.010 19100526
14. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress. Maitra M, Wang Y, Gerard RD, Mendelson CR, Garcia CK, J Biol Chem 2010 285 22103 22113 10.1074/jbc.M110.121467 20466729
15. Telomere diseases. Calado RT, Young NS, N Engl J Med 2009 361 2353 2365 10.1056/NEJMra0903373 20007561
16. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenital. Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I, Nature 2001 413 432 435 10.1038/35096585 11574891 (Pubitemid 32928599)
17. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW, Proc Natl Acad Sci USA 2005 102 15960 15964 10.1073/pnas.0508124102 16247010 (Pubitemid 41552850)
18. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK, Proc Natl Acad Sci USA 2007 104 7552 7557 10.1073/pnas.0701009104 17460043 (Pubitemid 47185944)
19. Telomere shortening in familial and sporadic pulmonary fibrosis. Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL, Garcia CK, Am J Respir Crit Care Med 2008 178 729 737 10.1164/rccm.200804-550OC 18635888
20. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Alder JK, Chen JJ, Lancaster L, Danoff S, Su SC, Cogan JD, Vulto I, Xie M, Qi X, Tuder RM, Phillips JA, Lansdorp PM, Loyd JE, Armanios MY, Proc Natl Acad Sci USA 2008 105 13051 13056 10.1073/pnas.0804280105 18753630
21. Role of diabetes mellitus and gastro-oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Gribbin J, Hubbard R, Smith C, Respir Med 2009 103 927 931 10.1016/j.rmed.2008.11.001 19058956
22. A common MUC5B promoter polymorphism and pulmonary fibrosis. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, Schwartz DA, N Engl J Med 2011 364 1503 1512 10.1056/NEJMoa1013660 21506741
23. Idiopathic pulmonary fibrosis. King TE, Pardo A, Selman M, Lancet 2011 378 1949 1961 10.1016/S0140-6736(11)60052-4 21719092
24. Genetics in pulmonary fibrosis-familial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis. Lawson WE, Loyd JE, Degryse AL, Am J Med Sci 2011 341 439 443 10.1097/MAJ.0b013e31821a9d7a 21613931
25. Statement on sarcoidosis. Joint statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999 160 736 755 10430755
26. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG task force. Baughman RP, Nagai S, Balter M, Costabel U, Drent M, du Bois R, Grutters JC, Judson MA, Lambiri I, Lower EE, Muller-Quernheim J, Prasse A, Rizzato G, Rottoli P, Spagnolo P, Teirstein A, Sarcoidosis Vasc Diffuse Lung Dis 2011 28 56 64 21796892
27. Epidemiology of familial sarcoidosis in UK. McGrath DS, Daniil Z, Foley P, du Bois JL, Lympany PA, Cullinan P, du Bois RM, Thorax 2000 55 751 754 10.1136/thorax.55.9.751 10950893 (Pubitemid 30660902)
28. Familial sarcoidosis in Finland and Hokkaido, Japan-a comparative study. Pietinalho A, Ohmichi M, Hirasawa M, Hiraga Y, Löfroos AB, Selroos O, Respir Med 1999 93 408 412 10.1053/rmed.1999.0579 10464823 (Pubitemid 29265351)
29. Familial risk ratio of sarcoidosis in African-American sibs and parents. Rybicki BA, Kirkey KL, Major M, Maliarik MJ, Popovich J, Chase GA, Iannuzzi MC, Am J Epidemiol 2001 153 188 193 10.1093/aje/153.2.188 11159165 (Pubitemid 32060611)
30. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Rybicki BA, Iannuzzi MC, Frederick MM, Thompson BW, Rossman MD, Bresnitz EA, Terrin ML, Moller DR, Barnard J, Baughman RP, DePalo L, Hunninghake G, Johns C, Judson MA, Knatterud GL, McLennan G, Newman LS, Rabin DL, Rose C, Teirstein AS, Weinberger SE, Yeager H, Cherniack R, ACCESS Research Group, Am J Respir Crit Care Med 2001 164 2085 2091 11739139 (Pubitemid 34020250)
31. Familial associations in sarcoidosis. A report to the research committee of the British thoracic and tuberculosis association. Tubercle 1973 54 87 98 4766014
32. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Rybicki BA, Major M, Popovich J, Maliarik MJ, Iannuzzi MC, Am J Epidemiol 1997 145 234 241 10.1093/oxfordjournals.aje.a009096 9012596
33. The mode of presentation of sarcoidosis in Finland and Hokkaido, Japan. A comparative analysis of 571 Finnish and 686 Japanese patients. Pietinalho A, Ohmichi M, Hiraga Y, Löfroos AB, Selroos O, Sarcoidosis Vasc Diffuse Lung Dis 1996 13 159 166 8893386 (Pubitemid 26332094)
34. Chemokine gene polymorphisms in idiopathic anterior uveitis. Yeo TK, Ahad MA, Kuo NW, Spagnolo P, Menezo V, Lympany P, Lightman S, Cytokine 2006 35 29 35 10.1016/j.cyto.2006.07.004 16950632 (Pubitemid 44485532)
35. HLA antigens in sarcoidosis. Brewerton DA, Cockburn C, James DC, James DG, Neville E, Clin Exp Immunol 1977 27 227 229 849654 (Pubitemid 8035688)
36. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Rossman MD, Thompson B, Frederick M, Maliarik M, Rybicki BA, Pandey GP, Newman LS, Magira E, Beznik-Cizman B, Monos D, ACCESS Group, Am J Hum Genet 2003 73 720 735 10.1086/378097 14508706 (Pubitemid 37271878)
37. Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African-Americans. Iannuzzi MC, Maliarik MJ, Poisson LM, Rybicki BA, Am J Respir Crit Care Med 2003 167 1225 1231 10.1164/rccm.200209-1097OC 12615619 (Pubitemid 36555094)
38. HLA class II amino acid epitopes as susceptibility markers of sarcoidosis. Voorter CE, Amicosante M, Berretta F, Groeneveld L, Drent M, van den Berg-Loonen EM, Tissue Antigens 2007 70 18 27 10.1111/j.1399-0039.2007. 00842.x 17559577 (Pubitemid 46890274)
39. Environmental triggers and susceptibility factors in idiopathic granulomatous diseases. Spagnolo P, Richeldi L, du Bois RM, Semin Respir Crit Care Med 2008 29 610 619 10.1055/s-0028-1101271 19221959
40. HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis. Sato H, Grutters JC, Pantelidis P, Mizzon AN, Ahmad T, Van Houte AJ, Lammers JW, Van Den Bosch JM, Welsh KI, du Bois RM, Am J Respir Cell Mol Biol 2002 27 406 412 12356573
41. Role of genetics in susceptibility and outcome of sarcoidosis. Grunewald J, Semin Respir Crit Care Med 2010 31 380 389 10.1055/s-0030-1262206 20665388
42. Genetics of sarcoidosis. Spagnolo P, du Bois RM, Clin Dermatol 2007 25 242 249 10.1016/j.clindermatol.2007.03.001 17560301 (Pubitemid 46863479)
43. Genome-wide association study identifies ANXA11 as a new susceptibility gene for sarcoidosis. Hofmann S, Franke A, Fischer A, Jacobs G, Nothnagel M, Gaede KI, Schurmann M, Muller-Quernheim J, Krawczak M, Rosenstiel P, Schreiber S, Nat Genet 2008 40 1103 1106 10.1038/ng.198 19165924
44. Genome-wide association analysis in sarcoidosis and Crohn's disease unravels a common susceptibility locus on 10p12.2. Franke A, Fischer A, Nothnagel M, Becker C, Grabe N, Till A, Lu T, Müller-Quernheim J, Wittig M, Hermann A, Balschun T, Hofmann S, Niemiec R, Schulz S, Hampe J, Nikolaus S, Nürnberg P, Krawczak M, Schürmann M, Rosenstiel P, Nebel A, Schreiber S, Gastroenterology 2008 135 1207 1215 10.1053/j.gastro.2008.07.017 18723019
45. A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1. Hofmann S, Fischer A, Till A, Müller-Quernheim J, Häsler R, Franke A, Gäde KI, Schaarschmidt H, Rosenstiel P, Nebel A, Schürmann M, Nothnagel M, Schreiber S, GenPhenReSa Consortium, Eur Respir J 2011 38 1127 1135 10.1183/09031936.00001711 21540310
46. Genome-wide association study of african and European americans implicates multiple shared and ethnic specific Loci in sarcoidosis susceptibility. Adrianto I, Lin CP, Hale JJ, Levin AM, Datta I, Parker R, Adler A, Kelly JA, Kaufman KM, Lessard CJ, Moser KL, Kimberly RP, Harley JB, Iannuzzi MC, Rybicki BA, Montgomery CG, Adrianto I, Lin CP, Hale JJ, Levin AM, Datta I, Parker R, Adler A, Kelly JA, Kaufman KM, Lessard CJ, Moser KL, Kimberly RP, Harley JB, Iannuzzi MC, Rybicki BA, Montgomery CG, PLoS One 2012 7 43907 Epub 2012 Aug 27 10.1371/journal.pone.0043907 22952805
47. Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Valentonyte R, Hampe J, Huse K, Rosenstiel P, Albrecht M, Stenzel A, Nagy M, Gaede KI, Franke A, Haesler R, Koch A, Lengauer T, Seegert D, Reiling N, Ehlers S, Schwinger E, Platzer M, Krawczak M, Müller-Quernheim J, Schürmann M, Schreiber S, Nat Genet 2005 37 357 364 10.1038/ng1519 15735647
48. The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. Rybicki BA, Walewski JL, Maliarik MJ, Kian H, Iannuzzi MC, Am J Hum Genet 2005 77 491 499 10.1086/444435 16080124 (Pubitemid 41192655)
49. BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation. Nguyen T, Liu XK, Zhang Y, Dong C, J Immunol 2006 176 7354 7360 16751379 (Pubitemid 43849036)
50. Association of the truncating splice site mutation in BTNL2 with multiple sclerosis is secondary to HLA-DRB1*15. Traherne JA, Barcellos LF, Sawcer SJ, Compston A, Ramsay PP, Hauser SL, Oksenberg JR, Trowsdale J, Hum Mol Genet 2006 15 155 161 16321988 (Pubitemid 43020113)
51. Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Orozco G, Eerligh P, Sánchez E, Zhernakova S, Roep BO, González-Gay MA, Lápez-Nevot MA, Callejas JL, Hidalgo C, Pascual-Salcedo D, Balsa A, González-Escribano MF, Koeleman BP, Martín J, Hum Immunol 2005 66 1235 1241 10.1016/j.humimm.2006.02.003 16690410
52. Association of the BTNL2 rs2076530 single nucleotide polymorphism with Graves' disease appears to be secondary to DRB1 exon 2 position beta74. Simmonds MJ, Heward JM, Barrett JC, Franklyn JA, Gough SC, Clin Endocrinol (Oxf) 2006 65 429 432 10.1111/j.1365-2265.2006.02586.x (Pubitemid 44414264)
53. Analysis of the BTNL2 truncating splice site mutation in tuberculosis, leprosy and Crohn's disease. Johnson CM, Traherne JA, Jamieson SE, Tremelling M, Bingham S, Parkes M, Blackwell JM, Trowsdale J, Tissue Antigens 2007 69 236 241 10.1111/j.1399-0039.2006.00795.x 17493147 (Pubitemid 46696945)
54. Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis. Spagnolo P, Sato H, Grutters JC, Renzoni EA, Marshall SE, Ruven HJT, Wells AU, Tzouvelekis A, van Moorsel CHM, van den Bosch JMM, du Bois RM, Welsh KI, Tissue Antigens 2007 70 219 227 10.1111/j.1399-0039.2007.00879.x 17661910 (Pubitemid 47106649)
55. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I, N Engl J Med 1998 338 1258 1264 10.1056/ NEJM199804303381803 9562579 (Pubitemid 28216579)
56. A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2. Wildenberg SC, Oetting WS, Almodávar C, Krumwiede M, White JG, King RA, Am J Hum Genet 1995 57 755 765 7573033
57. The cell biology of Hermansky-Pudlak syndrome: recent advaces. Di Pietro SM, Dell'Angelica EC, Traffic 2005 6 525 533 10.1111/j.1600-0854.2005.00299.x 15941404 (Pubitemid 40872355)
58. Lymphangioleiomyomatosis. Johnson SR, Eur Respir J 2006 5 1056 1065 (Pubitemid 44911122)
59. Tuberous sclerosis. Curatolo P, Bombardieri R, Jozwiak S, Lancet 2008 372 657 668 10.1016/S0140-6736(08)61279-9 18722871
60. Pulmonary lymphangiomyomatosis and tuberous sclerosis: comparison of radiographic and thin-section CT findings. Lenoir S, Grenier P, Brauner MW, Frija J, Remy-Jardin M, Revel D, Cordier JF, Radiology 1990 175 329 334 2326456 (Pubitemid 20135260)
61. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Science 1997 277 805 808 10.1126/science.277.5327.805 9242607 (Pubitemid 27366729)
62. Identification and characterization of the tuberous sclerosis gene on chromosome 16. The European Chromosome 16 Tuberous Sclerosis Consortium, Cell 1993 75 1305 1315 8269512
63. Birt-Hogg-Dubé syndrome: diagnosis and management. Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER, European BHD Consortium, Lancet Oncol 2009 10 1199 1206 10.1016/S1470-2045(09)70188-3 19959076
64. The tuberous sclerosis complex. Crino PB, Nathanson KL, Henske EP, N Engl J Med 2006 355 1345 1356 10.1056/NEJMra055323 17005952 (Pubitemid 44465463)
65. Dyskeratosis congenita as a disorder of telomere maintenance. Nelson ND, Bertuch AA, Mutat Res 2012 730 43 51 10.1016/j.mrfmmm.2011.06.008 21745483
66. Dyskeratosis congenita in all its forms. Dokal I, Br J Haematol 2000 110 768 779 10.1046/j.1365-2141.2000.02109.x 11054058
67. Genetic interstitial lung disease. Devine MS, Garcia CK, Clin Chest Med 2012 33 95 110 10.1016/j.ccm.2011.11.001 22365249
68. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Johnson SR, Cordier JF, Lazor R, Cottin V, Costabel U, Harari S, Reynaud-Gaubert M, Boehler A, Brauner M, Popper H, Bonetti F, Kingswood C, Review Panel of the ERS LAM Task Force, Eur Respir J 2010 35 14 26 10.1183/09031936.00076209 20044458
69. Sex-specific manifestations of Lofgren's Syndrome. Grunewald J, Eklund A, Am J Respir Crit Care Med 2007 175 40 44 17023727
70. Idiopathic pulmonary fibrosis: update on genetic discoveries. Garcia CK, Proc Am Thorac Soc 2011 8 158 162 10.1513/pats.201008-056MS 21543794
71. The next-generation of complex lung genetic studies. Yang IV, Schwartz DA, Am J Respir Crit Care Med 2012 Epub ahead of print
72. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC, National Institutes of Health Rare Lung Diseases Consortium MILES Trial Group, N Engl J Med 2011 364 1595 1606 10.1056/NEJMoa1100391 21410393