Clinics in Dermatology
Volume 25, Issue 3 , Pages 242-249 , May 2007

Genetics of sarcoidosis

  • Paolo Spagnolo, MD
    • ,
  • Roland M. du Bois, MD

      Affiliations

    • Corresponding Author InformationCorresponding author. Interstitial Lung Disease Unit, National Heart and Lung Institute/Imperial College of Science, Technology, and Medicine, London SW3 6LR, United Kingdom. Tel.: +44 20 7351 8327; fax: +44 20 7351 8336.

References 

  1. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336:1224–1234
  2. 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
  3. Rybicki BA, Maliarik MJ, Major M, Popovich J, Iannuzzi MC. Genetics of sarcoidosis. Clin Chest Med. 1997;18:707–717
  4. Grutters JC, Sato H, Welsh KI, du Bois RM. The importance of sarcoidosis genotype to lung phenotype. Am J Respir Cell Mol Biol. 2003;29(3 Suppl):S59-S62
  5. Lofgren S, Lundback H. The bilateral hilar lymphoma syndrome; a study of the relation to tuberculosis and sarcoidosis in 212 cases. Acta Med Scand. 1952;142:265–273
  6. Rossman MD, Thompson B, Frederick M, et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet. 2003;73:720–735
  7. Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science. 1993;262:242–244
  8. 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;164:2085–2091
  9. Demedts M, Wells AU, Anto JM, et al. Interstitial lung diseases: an epidemiological overview. Eur Respir J Suppl. 2001;32:2s–16s
  10. Pietinalho A, Ohmichi M, Hirasawa M, Hiraga Y, Lofroos AB, Selroos O. Familial sarcoidosis in Finland and Hokkaido, Japan—a comparative study. Respir Med. 1999;93:408–412
  11. Rybicki BA, Kirkey KL, Major M, et al. Familial risk ratio of sarcoidosis in African-American sibs and parents. Am J Epidemiol. 2001;153:188–193
  12. McGrath DS, Daniil Z, Foley P, et al. Epidemiology of familial sarcoidosis in the UK. Thorax. 2000;55:751–754
  13. Schurmann M, Lympany PA, Reichel P, et al. Familial sarcoidosis is linked to the major histocompatibility complex region. Am J Respir Crit Care Med. 2000;162(3 Pt 1):861–864
  14. Schurmann M, Reichel P, Muller-Myhsok B, Schlaak M, Muller-Quernheim J, Schwinger E. Results from a genome-wide search for predisposing genes in sarcoidosis. Am J Respir Crit Care Med. 2001;164:840–846
  15. Valentonyte R, Hampe J, Huse K, et al. Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet. 2005;37:357–364
  16. Stammers M, Rowen L, Rhodes D, Trowsdale J, Beck S. BTL-II: a polymorphic locus with homology to the butyrophilin gene family, located at the border of the major histocompatibility complex class II and class III regions in human and mouse. Immunogenetics. 2000;51:373–382
  17. Rybicki BA, Walewski JL, Maliarik MJ, Kian H, Iannuzzi MC. The BTNL2 gene and sarcoidosis susceptibility in African Americans and whites. Am J Hum Genet. 2005;77:491–499
  18. Cooke GS, Hill AV. Genetics of susceptibility to human infectious disease. Nat Rev Gene. 2001;2:967–977
  19. Martinetti M, Luisetti M, Cuccia M. HLA and sarcoidosis: new pathogenetic insights. Sarcoidosis Vasc Diffuse Lung Dis. 2002;19:83–95
  20. McGrath DS, Goh N, Foley PJ, du Bois RM. Sarcoidosis: genes and microbes—soil or seed?. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18:149–164
  21. McIntyre JA, McKee KT, Loadholt CB, Mercurio S, Lin I. Increased HLA-B7 antigen frequency in South Carolina blacks in association with sarcoidosis. Transplant Proc. 1977;9(1 Suppl 1):173–176
  22. Ina Y, Takada K, Yamamoto M, Morishita M, Senda Y, Torii Y. HLA and sarcoidosis in the Japanese. Chest. 1989;95:1257–1261
  23. Smith MJ, Turton CW, Mitchell DN, Turner-Warwick M, Morris LM, Lawler SD. Association of HLA B8 with spontaneous resolution in sarcoidosis. Thorax. 1981;36:296–298
  24. Olenchock SA, Heise ER, Marx JJ, et al. HLA-B8 in sarcoidosis. Ann Allergy. 1981;47:151–153
  25. Hedfors E, Lindstrom F. HLA-B8/DR3 in sarcoidosis. Correlation to acute onset disease with arthritis. Tissue Antigens. 1983;22:200–203
  26. Guyatt GH, Bensen WG, Stolmon LP, Fagnilli L, Singal DP. HLA-B8 and erythema nodosum. Can Med Assoc J. 1982;127:1005–1006
  27. Gardner J, Kennedy HG, Hamblin A, Jones E. HLA associations in sarcoidosis: a study of two ethnic groups. Thorax. 1984;39:19–22
  28. Kremer JM. Histologic findings in siblings with acute sarcoid arthritis: association with the B8, DR3 phenotype. J Rheumatol. 1986;13:593–597
  29. Krause A, Goebel KM. Class II MHC antigen (HLA-DR3) predisposes to sarcoid arthritis. J Clin Lab Immunol. 1987;24:25–27
  30. Grunewald J, Eklund A, Olerup O. Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients. Am J Respir Crit Care Med. 2004;169:696–702
  31. Sato H, Grutters JC, Pantelidis P, et al. HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis. Am J Respir Cell Mol Biol. 2002;27:406–412
  32. Ishihara M, Inoko H, Suzuki K, et al. HLA class II genotyping of sarcoidosis patients in Hokkaido by PCR-RFLP. Jpn J Ophthalmol. 1996;40:540–543
  33. Ishihara M, Ishida T, Inoko H, et al. HLA serological and class II genotyping in sarcoidosis patients in Japan. Jpn J Ophthalmol. 1996;40:86–94
  34. Nowack D, Goebel KM. Genetic aspects of sarcoidosis. Class II histocompatibility antigens and a family study. Arch Intern Med. 1987;147:481–483
  35. Swider C, Schnittger L, Bogunia-Kubik K, et al. TNF-alpha and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis. Eur Cytokine Netw. 1999;10:143–146
  36. Berlin M, Fogdell-Hahn A, Olerup O, Eklund A, Grunewald J. HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis. Am J Respir Crit Care Med. 1997;156:1601–1605
  37. Foley PJ, McGrath DS, Puscinska E, et al. Human leukocyte antigen–DRB1 position 11 residues are a common protective marker for sarcoidosis. Am J Respir Cell Mol Biol. 2001;25:272–277
  38. Foley PJ, Lympany PA, Puscinska E, Zielinski J, Welsh KI, du Bois RM. Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis. Am J Respir Crit Care Med. 1999;160:1009–1014
  39. Maliarik MJ, Chen KM, Major ML, et al. Analysis of HLA-DPB1 polymorphisms in African-Americans with sarcoidosis. Am J Respir Crit Care Med. 1998;158:111–114
  40. Rybicki BA, Maliarik MJ, Poisson LM, et al. The major histocompatibility complex gene region and sarcoidosis susceptibility in African Americans. Am J Respir Crit Care Med. 2003;167:444–449
  41. Iannuzzi MC, Maliarik MJ, Poisson LM, Rybicki BA. Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans. Am J Respir Crit Care Med. 2003;167:1225–1231
  42. Voorter CE, Drent M, vandenBerg-Loonen EM. Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602–DRB1*150101. Hum Immunol. 2005;66:826–835
  43. Grutters JC, Ruven HJT, Sato H, et al. MHC haplotype analysis in Dutch sarcoidosis patients presenting with Löfgren's syndrome. In:  Grutters JC editors. Genetic polymorphisms and phenotypes in sarcoidosis. Utrecht: Thesis University Utrecht; 2003;p. 85–96
  44. Grunewald J, Eklund A. Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis. Eur Respir J. 2001;17:1046–1048
  45. Takashige N, Naruse TK, Matsumori A, et al. Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens. 1999;54:191–193
  46. Naruse TK, Matsuzawa Y, Ota M, et al. HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis. Tissue Antigens. 2000;56:52–57
  47. Sharma OP. Vitamin D, calcium, and sarcoidosis. Chest. 1996;109:535–539
  48. Ohta M, Okabe T, Ozawa K, Urabe A, Takaku F. In vitro formation of macrophage-epithelioid cells and multinucleated giant cells by 1alpha,25-dihydroxyvitamin D3 from human circulating monocytes. Ann N Y Acad Sci. 1986;465:211–220
  49. Niimi T, Tomita H, Sato S, et al. Vitamin D receptor gene polymorphism in patients with sarcoidosis. Am J Respir Crit Care Med. 1999;160:1107–1109
  50. Guleva I, Seitzer U. Vitamin D receptor gene polymorphism in patients with sarcoidosis. Am J Respir Crit Care Med. 2000;162(2 Pt 1):760–761
  51. Rybicki BA, Maliarik MJ, Poisson LM, Iannuzzi MC. Sarcoidosis and granuloma genes: a family-based study in African-Americans. Eur Respir J. 2004;24:251–257
  52. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med. 1998;338:640–644
  53. Maliarik MJ, Chen KM, Sheffer RG, et al. The natural resistance–associated macrophage protein gene in African Americans with sarcoidosis. Am J Respir Cell Mol Biol. 2000;22:672–675
  54. Ishihara M, Ohno S, Mizuki N, et al. Genetic polymorphisms of the major histocompatibility complex–encoded antigen-processing genes TAP and LMP in sarcoidosis. Hum Immunol. 1996;45:105–110
  55. Muller-Quernheim J. Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J. 1998;12:716–738
  56. Seitzer U, Swider C, Stuber F, et al. Tumour necrosis factor alpha promoter gene polymorphism in sarcoidosis. Cytokine. 1997;9:787–790
  57. Grutters JC, Sato H, Pantelidis P, et al. Increased frequency of the uncommon tumor necrosis factor −857T allele in British and Dutch patients with sarcoidosis. Am J Respir Crit Care Med. 2002;165:1119–1124
  58. Hutyrova B, Pantelidis P, Drabek J, et al. Interleukin-1 gene cluster polymorphisms in sarcoidosis and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002;165:148–151
  59. Rybicki BA, Maliarik MJ, Malvitz E, et al. The influence of T cell receptor and cytokine genes on sarcoidosis susceptibility in African Americans. Hum Immunol. 1999;60:867–874
  60. Grutters JC, Sato H, Pantelidis P, et al. Analysis of IL6 and IL1A gene polymorphisms in UK and Dutch patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20:20–27
  61. Luster AD. Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med. 1998;338:436–445
  62. Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med. 2002;8:435–440
  63. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354:610–621
  64. Hizawa N, Yamaguchi E, Furuya K, Jinushi E, Ito A, Kawakami Y. The role of the C-C chemokine receptor 2 gene polymorphism V64I (CCR2-64I) in sarcoidosis in a Japanese population. Am J Respir Crit Care Med. 1999;159:2021–2023
  65. Petrek M, Drabek J, Kolek V, et al. CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis. Am J Respir Crit Care Med. 2000;162(3 Pt 1):1000–1003
  66. Michael NL, Louie LG, Rohrbaugh AL, et al. The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression. Nat Med. 1997;3:1160–1162
  67. Smith MW, Carrington M, Winkler C, et al. CCR2 chemokine receptor and AIDS progression. Nat Med. 1997;3:1052–1053
  68. Spagnolo P, Renzoni EA, Wells AU, et al. C-C chemokine receptor 2 and sarcoidosis: association with Löfgren's syndrome. Am J Respir Crit Care Med. 2003;68:1162–1166
  69. Valentonyte R, Hampe J, Croucher PJ, et al. Study of C-C chemokine receptor 2 alleles in sarcoidosis, with emphasis on family-based analysis. Am J Respir Crit Care Med. 2005;171:1136–1141
  70. Alkhatib G, Combadiere C, Broder CC, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–1958
  71. Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382:722–725
  72. Spagnolo P, Renzoni EA, Wells AU, et al. C-C chemokine receptor 5 gene variants in relation to lung disease in sarcoidosis. Am J Respir Crit Care Med. 2005;172:721–728
  73. Lieberman J. Enzymes in sarcoidosis. Angiotensin-converting-enzyme (ACE). Clin Lab Med. 1989;9:745–755
  74. Rigat B, Hubert C, henc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I–converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343–1346
  75. Furuya K, Yamaguchi E, Itoh A, et al. Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis. Thorax. 1996;51:777–780
  76. Maliarik MJ, Rybicki BA, Malvitz E, et al. Angiotensin-converting enzyme gene polymorphism and risk of sarcoidosis. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1566–1570
  77. Schurmann M, Reichel P, Muller-Myhsok B, et al. Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis. J Intern Med. 2001;249:77–83
  78. McGrath DS, Foley PJ, Petrek M, et al. ACE gene I/D polymorphism and sarcoidosis pulmonary disease severity. Am J Respir Crit Care Med. 2001;164:197–201
  79. Arbustini E, Grasso M, Leo G, et al. Polymorphism of angiotensin-converting enzyme gene in sarcoidosis. Am J Respir Crit Care Med. 1996;153:851–854
  80. Tomita H, Ina Y, Sugiura Y, et al. Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis. Am J Respir Crit Care Med. 1997;156:255–259

PII: S0738-081X(07)00055-7

doi: 10.1016/j.clindermatol.2007.03.001

Clinics in Dermatology
Volume 25, Issue 3 , Pages 242-249 , May 2007

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