Skip to main content
SpringerLink
Log in
Book cover

Scleroderma pp 29–44Cite as

Genetic Factors

  • Chapter
  • First Online:

  • 1680 Accesses

Abstract

Systemic sclerosis (SSc) is an orphan connective tissue disease. It is characterised by early vascular damage followed by both tissue and systemic fibrosis affecting many organs, including, in particular, the skin, lungs, heart, kidneys and digestive tract. The combination of environmental and stochastic factors converging upon individuals of a particular genetic background seems to contribute to the development of this disease. We will begin by considering various genetic approaches that can be applied to the study of multi-factorial diseases and will then move on to the principal factors implicated in this disease, which will be considered in greater detail.

This is a preview of subscription content, log in via an institution.

References

  1. Vitart V, Rudan I, Hayward C, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008;40:437–42.

    Article  PubMed  CAS  Google Scholar 

  2. Plomin R, Haworth CMA, Davis OSP. Common disorders are quantitative traits. Nat Rev Genet. 2009;10:872–8.

    Article  PubMed  CAS  Google Scholar 

  3. Repapi E, Sayer I, Wain LV, et al. Genome-wide association study identifies five loci associated with pulmonary function. Nat Genet. 2010;42:36–44.

    Article  PubMed  CAS  Google Scholar 

  4. Kochi Y, Suzuki A, Yamada R, Yamamoto K. Ethnogenetic heterogeneity of rheumatoid arthritis – implications for pathogenesis. Nat Rev Rheumatol. 2010;6:290–5.

    Article  PubMed  CAS  Google Scholar 

  5. Arnett FC, Cho M, Chatterjee S, et al. Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts. Arthritis Rheum. 2001;44:1359–62.

    Article  PubMed  CAS  Google Scholar 

  6. Feghali-Bostwick C, Medsger Jr TA, Wright TM. Analysis of systemic sclerosis in twins reveals low concordance for disease and high concordance for the presence of antinuclear antibodies. Arthritis Rheum. 2003;48:1956–63.

    Article  PubMed  Google Scholar 

  7. Zhou X, Tan FK, Xiong M, et al. Monozygotic twins clinically discordant for scleroderma show concordance for fibroblast gene expression profiles. Arthritis Rheum. 2005;52:3305–14.

    Article  PubMed  CAS  Google Scholar 

  8. Zhou X, Tan FK, Wang N, et al. Genome-wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence. Arthritis Rheum. 2003;48:2585–92.

    Article  PubMed  CAS  Google Scholar 

  9. Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, et al. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum. 2009;60:3807–14.

    Article  PubMed  CAS  Google Scholar 

  10. Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010;42:426–9.

    Article  PubMed  CAS  Google Scholar 

  11. Tan FK, Stivers DN, Foster MW, et al. Association of microsatellite markers near the fibrillin 1 gene on human chromosome 15q with scleroderma in a native American population. Arthritis Rheum. 1998;41:1729–37.

    Article  PubMed  CAS  Google Scholar 

  12. Tan FK, Wang N, Kuwana M, et al. Association of fibrillin 1 single-nucleotide polymorphism haplotypes with systemic sclerosis in Choctaw and Japanese populations. Arthritis Rheum. 2001;44:893–901.

    Article  PubMed  CAS  Google Scholar 

  13. Wipff J, Giraud M, Sibilia J, Mouthon L, Meyer O, Tiev K, et al. Polymorphic markers of the fibrillin-1 gene and systemic sclerosis in European Caucasian patients. J Rheumatol. 2008;35:643–9.

    PubMed  CAS  Google Scholar 

  14. Lemaire R, Bayle J, Lafyatis R. Fibrillin in Marfan syndrome and tight skin mice provides new insights into transforming growth factor-beta regulation and systemic sclerosis. Curr Opin Rheumatol. 2006;18:582–7.

    Article  PubMed  CAS  Google Scholar 

  15. Wipff J, Avouac J, Le Charpentier M, Varret M, Houtteman A, Ruiz B, et al. Dermal tissue and cellular expression of fibrillin-1 in diffuse cutaneous systemic sclerosis. Rheumatology (Oxford). 2010;49:657–61.

    Article  CAS  Google Scholar 

  16. Avila JJ, Lympani PA, Pantelidis P, et al. Fibronectin gene polymorphisms associated with fibrosing alveolitis in systemic sclerosis. Am J Respir Cell Mol Biol. 1999;20:106–12.

    PubMed  CAS  Google Scholar 

  17. Zhou X, Tan FK, Reveille JD, et al. Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma. Arthritis Rheum. 2002;46:2290–9.

    Article  Google Scholar 

  18. Lagan AL, Pantelidis P, Renzoni EA, et al. Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma. Rheumatology (Oxford). 2005;44:197–201.

    Article  CAS  Google Scholar 

  19. Zhou X, Tan FK, Guo X, Arnett FC. Attenuation of collagen production with small interfering RNA of SPARC in cultured fibroblasts from the skin of patients with scleroderma. Arthritis Rheum. 2006;54:2626–31.

    Article  PubMed  CAS  Google Scholar 

  20. Crilly A, Hamilton J, Jardine A, et al. Analysis of transforming growth factor-beta1 gene polymorphisms in patients with systemic sclerosis. Ann Rheum Dis. 2002;61:678–81.

    Article  PubMed  CAS  Google Scholar 

  21. Ohtsuka T, Yamakage A, Yamazaki S. The polymorphism of transforming growth factor-beta1 in Japanese patients with systemic sclerosis. Br J Dermatol. 2002;147:458–63.

    Article  PubMed  CAS  Google Scholar 

  22. Sugiura Y, Banno S, Matsumoto Y, et al. Transforming growth factor-beta1 polymorphism in patients with systemic sclerosis. J Rheumatol. 2003;30:1520–3.

    PubMed  CAS  Google Scholar 

  23. Lee EB, Kim JY, Lee YJ, et al. Transforming growth factor-beta1 polymorphism in Korean patients with systemic sclerosis. Tissue Antigens. 2004;63:491–5.

    Article  PubMed  CAS  Google Scholar 

  24. Zhou X, Tan FK, Stivers DN, et al. Microsatellites and intragenic polymorphisms of transforming growth factor-beta and platelet-derived growth factor and their receptor genes in Native Americans with systemic sclerosis (scleroderma): a preliminary analysis showing no genetic association. Arthritis Rheum. 2000;43:1068–73.

    Article  PubMed  CAS  Google Scholar 

  25. Fonseca C, Lindahl GE, Ponticos M, Sestini P, Renzoni EA, Holmes AM, et al. A polymorphism in the CTGF promoter region associated with systemic sclerosis. N Engl J Med. 2007;357:1210–20.

    Article  PubMed  CAS  Google Scholar 

  26. Rueda B, Broen J, Simeon C, Hesselstrand R, Diaz B, Suárez H, et al. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet. 2009;18:2071–7.

    Article  PubMed  CAS  Google Scholar 

  27. Gourh P, Agarwal SK, Divecha D, Assassi S, Paz G, Arora-Singh RK, et al. Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum. 2009;60:3794–806.

    Article  PubMed  CAS  Google Scholar 

  28. Rueda B, Simeon C, Hesselstrand R, Herrick A, Worthington J, Ortego-Centeno N, et al. A large multicenter analysis of CTGF −945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype. Ann Rheum Dis. 2009;68:1618–20.

    Article  PubMed  CAS  Google Scholar 

  29. Kawaguchi Y, Tochimoto A, Ichikawa N, et al. Association of IL1A gene polymorphisms with susceptibility to and severity of systemic sclerosis in the Japanese population. Arthritis Rheum. 2003;48:186–92.

    Article  PubMed  CAS  Google Scholar 

  30. Hutyrova B, Lukac J, Bosak V, et al. Interleukin 1 alpha single-nucleotide polymorphism associated with systemic sclerosis. J Rheumatol. 2004;31:81–4.

    PubMed  CAS  Google Scholar 

  31. Lambert NC, Distler O, Muller-Ladner U, et al. HLA-DQA1 *0501 is associated with diffuse systemic sclerosis in Caucasian men. Arthritis Rheum. 2000;43:2005–10.

    Article  PubMed  CAS  Google Scholar 

  32. Kuwana M, Inoko H, Kameda H, et al. Association of human leucocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis. Intern Med. 1999;38:336–44.

    Article  PubMed  CAS  Google Scholar 

  33. Ueki A, Isozaki Y, Tomokuni A, et al. Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct sequence in the HLA-DQB1 domain. Immunobiology. 2001;204:458–65.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. Arnett FC, Gourh P, Shete S, Ahn CW, Honey RE, Agarwal SK, et al. Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls. Ann Rheum Dis. 2010;69:822–7.

    Article  PubMed  CAS  Google Scholar 

  36. Gourh P, Agarwal SK, Martin E, Divecha D, Rueda B, Bunting H, et al. Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations. J Autoimmun. 2010;34:155–62.

    Article  PubMed  CAS  Google Scholar 

  37. Bossini-Castillo L, Broen JC, Simeon CP, Beretta L, Vonk MC, Ortego-Centeno N, et al. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Ann Rheum Dis. 2011;70:638–41.

    Article  PubMed  CAS  Google Scholar 

  38. Tan FK, Zhou X, Mayes MD, Gourh P, Guo X, Marcum C, Jin L, Arnett FC. Signatures of differentially regulated interferon gene expression and vasculotropism in the peripheral blood cells of systemic sclerosis patients. Rheumatology. 2006;45:694–702.

    Article  PubMed  CAS  Google Scholar 

  39. York MR, Nagai T, Mangini AJ, Lemaire R, van Seventer JM, Lafyatis R. A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists. Arthritis Rheum. 2007;56:1010–20.

    Article  PubMed  CAS  Google Scholar 

  40. Assassi S, Mayes MD, Arnett FC, Gourh P, Agarwal SK, McNearney TA, et al. Systemic sclerosis and lupus: points in an interferon-mediated continuum. Arthritis Rheum. 2010;62:589–98.

    Article  PubMed  CAS  Google Scholar 

  41. Tan FK, Guo X, Arnett FC, Zhou X. Attenuation of collagen production with small interfering RNA of SPARC in cultured fibroblasts from the skin of patients with scleroderma. Arthritis Rheum. 2006;54:2626–31.

    Article  PubMed  Google Scholar 

  42. Farina GA, York MR, Di Marzio M, Collins CA, Meller S, Homey B, Rifkin IR, Marshak-Rothstein A, Radstake TR, Lafyatis R. Poly(I:C) drives type I IFN- and TGFβ-mediated inflammation and dermal fibrosis simulating altered gene expression in systemic sclerosis. J Invest Dermatol. 2010;130:2583–93.

    Article  PubMed  CAS  Google Scholar 

  43. Agarwal SK, Wu M, Livingston CK, Parks DH, Mayes MD, Arnett FC, Tan FK. Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts. Arthritis Res Ther. 2011;13:R3.

    Article  PubMed  CAS  Google Scholar 

  44. Dieudé P, Guedj M, Wipff J, Ruiz B, Hachulla E, Diot E, et al. STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. Arthritis Rheum. 2009;60:2472–9.

    Article  PubMed  Google Scholar 

  45. Ito I, Kawaguchi Y, Kawasaki A, Hasegawa M, Ohashi J, Hikami K, et al. Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population. Arthritis Rheum. 2009;60:1845–50.

    Article  PubMed  CAS  Google Scholar 

  46. Dieudé P, Guedj M, Wipff J, Ruiz B, Riemekasten G, Airo P, Melchers I, 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.

    Article  PubMed  Google Scholar 

  47. Dieudé P, Guedj M, Wipff J, Avouac J, Fajardy I, Diot E, et al. Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: a new perspective for pulmonary fibrosis. Arthritis Rheum. 2009;60:225–33.

    Article  PubMed  Google Scholar 

  48. Rueda B, Gourh P, Broen J, Agarwal SK, Simeon CP, Ortego-Centeno N, et al. BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians. Ann Rheum Dis. 2010;69:700–5.

    Article  PubMed  CAS  Google Scholar 

  49. Dieude P, Wipff J, Guedj M, Ruiz B, Melchers I, Hachulla E, et al. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis Rheum. 2009;60:3447–54.

    Article  PubMed  CAS  Google Scholar 

  50. Tsuchiya N, Kawasaki A, Hasegawa M, Fujimoto M, Takehara K, Kawaguchi Y, et al. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann Rheum Dis. 2009;68:1375–6.

    Article  PubMed  CAS  Google Scholar 

  51. Avouac J, Fürnrohr BG, Tomcik M, Palumbo K, Zerr P, Horn A, et al. Inactivation of the transcription factor STAT4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis. Arthritis Rheum. 2011;63:800–9.

    Article  PubMed  CAS  Google Scholar 

  52. Almasi S, Erfani N, Mojtahedi Z, Rajaee A, Ghaderi A. Association of CTLA-4 gene promoter polymorphisms with systemic sclerosis in Iranian population. Genes Immun. 2006;7:401–6.

    Article  PubMed  CAS  Google Scholar 

  53. Abdallah AM, Renzoni EA, Anevlavis S, et al. A polymorphism in the promoter region of the CD86 (B7.2) gene is associated with systemic sclerosis. Int J Immunogenet. 2006;33:155–61.

    Article  PubMed  CAS  Google Scholar 

  54. Gourh P, Tan FK, Assassi S, et al. Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis. Arthritis Rheum. 2006;54:3945–53.

    Article  PubMed  CAS  Google Scholar 

  55. Dieude P, Guedj M, Wipff J, Avouac J, Hachulla E, Diot E, et al. The PTPN22 620 W allele confers susceptibility to systemic sclerosis: findings of a large case-control study of European Caucasians and a meta-analysis. Arthritis Rheum. 2008;58:2183–8.

    Article  PubMed  CAS  Google Scholar 

  56. Dieudé P, Guedj M, Truchetet ME, Wipff J, Revillod L, Riemekasten G, et al. Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis. Arthritis Rheum. 2011;63(4):1097–105. doi: 10.1002/art.30204.

    Article  PubMed  Google Scholar 

  57. Gorman CL, Russell AI, Zhang Z, Cunninghame Graham D, Cope AP, Vyse TJ. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J Immunol. 2008;180:1060–70.

    PubMed  CAS  Google Scholar 

  58. Gourh P, Arnett FC, Tan FK, Assassi S, Divecha D, Paz G, et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann Rheum Dis. 2010;69:550–5.

    Article  PubMed  CAS  Google Scholar 

  59. Ito I, Kawaguchi Y, Kawasaki A, Hasegawa M, Ohashi J, Kawamoto M, et al. Association of the FAM167A-BLK region with systemic sclerosis. Arthritis Rheum. 2010;62:890–5.

    Article  PubMed  CAS  Google Scholar 

  60. Tsuchiya N, Kuroki K, Fujimoto M, et al. Association of a functional CD19 polymorphism with susceptibility to systemic sclerosis. Arthritis Rheum. 2004;50:4002–7.

    Article  PubMed  CAS  Google Scholar 

  61. Pandey JP, Takeuchi F. TNF-alpha and TNF-beta gene polymorphisms in systemic sclerosis. Hum Immunol. 1999;60:1128–30.

    Article  PubMed  CAS  Google Scholar 

  62. Takeuchi F, Nabeta H, Fussel M, et al. Association of tumor TNFa13 microsatellite with systemic sclerosis in Japanese patients. Ann Rheum Dis. 2000;59:293–6.

    Article  PubMed  CAS  Google Scholar 

  63. Sato H, Lagan AL, Alexopoulo C, et al. The TNF-863A allele strongly associates with anticentromere positivity in scleroderma. Arthritis Rheum. 2004;50:558–64.

    Article  PubMed  CAS  Google Scholar 

  64. Tolusso B, Fabris M, Caporali M, et al. 238 and +489 TNF-alpha along with TNFR-II gene polymorphisms associated with the diffuse phenotype in patients with systemic sclerosis. Immunol Lett. 2005;96:103–8.

    Article  PubMed  CAS  Google Scholar 

  65. Broen J, Gourh P, Rueda B, Coenen M, Mayes M, Martin J, et al. The FAS -670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes. Arthritis Rheum. 2009;60:3815–20.

    Article  PubMed  CAS  Google Scholar 

  66. Liakouli V, Manetti M, Pacini A, Tolusso B, Fatini C, Toscano A, et al. The -670 G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis. Ann Rheum Dis. 2009;68:584–90.

    Article  PubMed  CAS  Google Scholar 

  67. Dieudé P, Guedj M, Wipff J, Ruiz B, Riemekasten G, Matucci-Cerinic M, et al. Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population. Ann Rheum Dis. 2010;69(11):1958–64.

    Article  Google Scholar 

  68. Riccieri V, Parisi G, Spadaro A, et al. Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. Genes Immun. 2005;6:274–8.

    Article  Google Scholar 

  69. Granel B, Allanore Y, Chevillard C, et al. IL13RA2 Gene polymorphisms are associated with systemic sclerosis. J Rheumatol. 2006;33:2015–9.

    PubMed  CAS  Google Scholar 

  70. Granel B, Chevillard C, Allanore Y, et al. Evaluation of interleukin 13 polymorphisms in systemic sclerosis. Immunogenetics. 2006;58:693–9.

    Article  PubMed  CAS  Google Scholar 

  71. Karrer S, Kathrin Bosserhoff A, Weiderer P, et al. The −2518 promotor polymorphism in the MCP-1 gene is associated with systemic sclerosis. J Invest Dermatol. 2005;124:92–8.

    Article  PubMed  CAS  Google Scholar 

  72. Radstake TR, Vonk MC, Dekkers M, Schijvenaars MM, Treppichio WL, Lafyatis R, et al. The -2518A>G promoter polymorphism in the CCL2 gene is not associated with systemic sclerosis susceptibility or phenotype: results from a multicenter study of European Caucasian patients. Hum Immunol. 2009;70:130–3.

    Article  PubMed  CAS  Google Scholar 

  73. Wu SP, Leng L, Feng Z, et al. Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of scleroderma. Arthritis Rheum. 2006;54:3661–9.

    Article  PubMed  CAS  Google Scholar 

  74. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):13S–24.

    Article  PubMed  CAS  Google Scholar 

  75. Tew MB, Arnett FC, Reveille JD, et al. Mutations of bone morphogenic protein receptor 2 (BMPR2) are not found in patients with primary pulmonary hypertension and underlying connective tissue disease. Arthritis Rheum. 2002;46:2829–30.

    Article  PubMed  Google Scholar 

  76. Morse J, Barst R, Horn E, et al. Pulmonary hypertension in scleroderma spectrum of disease: lack of bone morphogenic protein receptor 2 mutations. J Rheumatol. 2002;29:2379–81.

    PubMed  Google Scholar 

  77. Wipff J, Kahan A, Hachulla E, et al. Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary hypertension. Rheumatology. 2007;46:622–5.

    Article  PubMed  CAS  Google Scholar 

  78. Fatini C, Gersini F, Sticchi E, et al. High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis. Am J Med. 2002;112:539–43.

    Article  Google Scholar 

  79. Allanore Y, Borderie D, Lemaréchal H, Ekindjian OG, Kahan A. Lack of association of eNOS (G894T) and p22phox NADPH oxidase sub-unit (C242T) polymorphisms with systemic sclerosis in a cohort of French Caucasian patients. Clin Chim Acta. 2004;350:51–5.

    Article  PubMed  CAS  Google Scholar 

  80. Assassi S, Mayes MD, McNearney T, et al. Polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in systemic sclerosis. Am J Med. 2005;118:907–11.

    Article  PubMed  CAS  Google Scholar 

  81. Kawaguchi Y, Tochimoto A, Hara M, et al. NOS2 polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity. Arthritis Res Ther. 2006;8:R104.

    Article  PubMed  Google Scholar 

  82. Wipff J, Gallier G, Dieude P, Avouac J, Tiev K, Hachulla E, et al. Angiotensin-converting enzyme gene does not contribute to genetic susceptibility to systemic sclerosis in European Caucasians. J Rheumatol. 2009;36:337–40.

    Article  PubMed  Google Scholar 

  83. Fonseca C, Renzoni E, Sestini P, et al. Endothelin axis polymorphisms in patients with scleroderma. Arthritis Rheum. 2006;54:3034–42.

    Article  PubMed  CAS  Google Scholar 

  84. Allanore Y, Borderie D, Airo P, et al. Lack of association between 3 vascular endothelial growth factor gene polymorphisms and systemic sclerosis: results from a multicenter EUSTAR study of European Caucasian patients. Ann Rheum Dis. 2007;66:257–9.

    Article  PubMed  CAS  Google Scholar 

  85. Ballestar E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol. 2011;7:263–71.

    Article  PubMed  CAS  Google Scholar 

  86. Jüngel A, Ospelt C, Gay S. What can we learn from epigenetics in the year 2009? Curr Opin Rheumatol. 2010;22:284–92.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, Cochin, Paris Descartes University, Paris, France

    Yannick Allanore MD, PhD

  2. Department of Internal Medicine, Division of Rheumatology, UT Houston Medical School, Houston, TX, USA

    Filemon K. Tan MD, PhD

Authors
  1. Yannick Allanore MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Filemon K. Tan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yannick Allanore MD, PhD .

Editor information

Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, E. Huron Street 240, Chicago, 60611-2909, Illinois, USA

    John Varga

  2. Royal Free and University College, Medical School, University College London, Rowland Street, London, NW3 2PF, United Kingdom

    Christopher P. Denton

  3. School of Medicine, Div. Rheumatology, Johns Hopkins University, Eastern Avenue 5200, Baltimore, 21224, Maryland, USA

    Fredrick M. Wigley

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Allanore, Y., Tan, F.K. (2012). Genetic Factors. In: Varga, J., Denton, C., Wigley, F. (eds) Scleroderma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-5774-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-5774-0_5

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5773-3

  • Online ISBN: 978-1-4419-5774-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation