Zeitschrift für Rheumatologie

, Volume 68, Issue 9, pp 758–762

Familiäre Häufung, genetische Wurzeln und Erkenntniszugewinn in der Pathogenese von Autoimmunerkrankungen

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Zusammenfassung

Genomweite Screening-Studien haben zu einem rasanten Erkenntniszuwachs über genetische Ursachen von Autoimmunerkrankungen geführt. Die identifizierten Gene sind Indikatoren für pathogenetisch relevante Signalwege und können zur Identifizierung therapeutischer Angriffspunkte beitragen.

Schlüsselwörter

Autoimmunerkrankungen Rheumatoide Arthritis Gentypisierung Diagnostische Marker Genpolymorphismus 

Familial clustering, genetic roots and insights into the pathogenesis of autoimmune diseases

Abstract

Genome-wide association studies have dramatically increased our knowledge about the genetic contribution to autoimmune diseases. The identified genes are indicators for signal transduction pathways involved in disease pathogenesis and could contribute to potential new therapeutic approaches.

Keywords

Autoimmune diseases Rheumatoid arthritis Gene typing Diagnostic markers Gene polymorphism 

Literatur

  1. 1.
    Silman AJ, MacGregor AJ, Thomson W et al (1993) Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol 32:903–907CrossRefPubMedGoogle Scholar
  2. 2.
    Aho K, Koskenvuo M, Tuominen J et al (1986) Occurrence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 13:899–902PubMedGoogle Scholar
  3. 3.
    MacGregor AJ, Snieder H, Rigby AS et al (2000) Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 43:30–37CrossRefPubMedGoogle Scholar
  4. 4.
    Panayi GS, Wooley P, Batchelor JR (1978) Genetic basis of rheumatoid disease: HLA antigens, disease manifestations, and toxic reactions to drugs. Br Med J 2:1326–1328CrossRefPubMedGoogle Scholar
  5. 5.
    Stastny P (1978) Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 298:869–871PubMedCrossRefGoogle Scholar
  6. 6.
    Wagner U, Kaltenhäuser S, Sauer H et al (1997) HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. Arthritis Rheum 40:341–351CrossRefPubMedGoogle Scholar
  7. 7.
    Weyand CM, Xie C, Goronzy JJ (1992) Homozygosity for the HLA-DRB1 allele selects for extraarticular manifestations in rheumatoid arthritis. J Clin Invest 89:2033–2039CrossRefPubMedGoogle Scholar
  8. 8.
    Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213CrossRefPubMedGoogle Scholar
  9. 9.
    Johnsen AK, Plenge RM, Butty V et al (2008) A broad analysis of IL1 polymorphism and rheumatoid arthritis. Arthritis Rheum 58:1947–1957CrossRefPubMedGoogle Scholar
  10. 10.
    Ueda H, Howson JM, Esposito L et al (2003) Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423:506–511CrossRefPubMedGoogle Scholar
  11. 11.
    Suzuki A, Yamada R, Chang X et al (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34:395–402CrossRefPubMedGoogle Scholar
  12. 12.
    Begovich AB, Carlton VE, Honigberg LA et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330–337CrossRefPubMedGoogle Scholar
  13. 13.
    Hoppe B, Häupl T, Gruber R et al (2006) Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study. Arthritis Res Ther 8:R34CrossRefPubMedGoogle Scholar
  14. 14.
    Harris ML, Darrah E, Lam GK et al (2008) Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis. Arthritis Rheum 58:1958–1967CrossRefPubMedGoogle Scholar
  15. 15.
    Bottini N, Musumeci L, Alonso A et al (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36:337–338CrossRefPubMedGoogle Scholar
  16. 16.
    Criswell LA, Pfeiffer KA, Lum RF et al (2005) Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620 W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 76:561–571CrossRefPubMedGoogle Scholar
  17. 17.
    Kyogoku C, Langefeld CD, Ortmann WA et al (2004) Genetic association of the R620 W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 75:504–507CrossRefPubMedGoogle Scholar
  18. 18.
    Kochi Y, Yamada R, Suzuki A et al (2005) A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 37:478–485CrossRefPubMedGoogle Scholar
  19. 19.
    Plenge RM, Seielstad M, Padyukov L et al (2007) TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. N Engl J Med 357:1199–1209CrossRefPubMedGoogle Scholar
  20. 20.
    Kurreeman FA, Padyukov L, Marques RB et al (2007) A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS Med 4:e278CrossRefPubMedGoogle Scholar
  21. 21.
    Orozco G, Alizadeh BZ, Delgado-Vega AM et al (2008) Association of STAT4 with rheumatoid arthritis: a replication study in three European populations. Arthritis Rheum 58:1974–1980CrossRefPubMedGoogle Scholar
  22. 22.
    Raychaudhuri S, Remmers EF, Lee AT et al (2008) Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet 40:1216–1223CrossRefPubMedGoogle Scholar
  23. 23.
    Suzuki A, Yamada R, Kochi Y et al (2008) Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population. Nat Genet 40:1224–1229CrossRefPubMedGoogle Scholar
  24. 24.
    Barton A, Thomson W, Ke X et al (2008) Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13. Nat Genet 40:1156–1159CrossRefPubMedGoogle Scholar
  25. 25.
    Orozco G, Hinks A, Eyre S et al (2009) Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23. Hum Mol Genet 18:2693–2699CrossRefPubMedGoogle Scholar
  26. 26.
    Plenge RM, Cotsapas C, Davies L et al (2007) Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 39:1477–1482CrossRefPubMedGoogle Scholar
  27. 27.
    Hom G, Graham RR, Modrek B et al (2008) Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358:900–909CrossRefPubMedGoogle Scholar
  28. 28.
    International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcón-Riquelme ME et al (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40:204–210CrossRefGoogle Scholar
  29. 29.
    Musone SL, Taylor KE, Lu TT et al (2008) Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 40(9):1062–1064CrossRefPubMedGoogle Scholar
  30. 30.
    Graham RR, Cotsapas C, Davies L et al (2008) Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet [E-pub ahead of print Aug 1]Google Scholar
  31. 31.
    Wassmuth R, Wagner U (2002) Prognostic use of human leukocyte antigen 31.notyping for rheumatoid arthritis susceptibility, disease course, and clinical stratification. Rheum Dis Clin North Am 28:17–37CrossRefPubMedGoogle Scholar
  32. 32.
    Kaltenhäuser S, Pierer M, Arnold S et al (2007) Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis. Rheumatology (Oxford) 46:100–104Google Scholar
  33. 33.
    Rossol M, Pierer M, Arnold S et al (2009) Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis. Arthritis Res Ther 11:R91CrossRefPubMedGoogle Scholar
  34. 34.
    Wagner U, Kaltenhäuser S, Pierer M et al (2003) Prospective analysis of the impact of HLA-DR and -DQ on joint destruction in recent-onset rheumatoid arthritis. Rheumatology (Oxford) 42:553–562Google Scholar
  35. 35.
    Goldstein DB (2009) Common genetic variation and human traits. N Engl J Med 360:1696–1698CrossRefPubMedGoogle Scholar
  36. 36.
    Weedon MN, Lango H, Lindgren CM et al (2008) Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 40:575–583CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2009

Authors and Affiliations

  1. 1.Medizinische Klinik II, Sektion RheumatologieUniversität LeipzigLeipzigDeutschland

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