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The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid arthritis

Genes & Immunity volume 3, pages 110–113 (2002)Cite this article

Abstract

We considered that the constitutive over-expression by cultured rheumatoid arthritis (RA) fibroblast-lineage synoviocytes of genes like IGFBP5 could indicate new candidate susceptibility genes. IGFBP5 is located in a region where an insulin-dependent diabetes mellitus (IDDM) susceptibility locus, IDDM13 (2q33-q36), has been mapped. Previous evidence that non-MHC IDDM loci overlap RA susceptibility loci made IGFBP5 and its region an interesting candidate locus which was tested for linkage. Forty-nine sibships (2–4 affected siblings per sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM interval in the IGFBP5/IDDM13 region. Both the two-point LOD scores and a ‘nonparametric’ allele-sharing analysis revealed no evidence for linkage (max LOD = 0.54, P = 0.5, respectively). Adjustments for the presence of ‘shared-epitope’ alleles did not significantly change the LOD scores. These results suggest that, despite the involvement of the 2q33-q36 chromosomal region in another organ-specific autoimmune disease, it is unlikely that this region harbors a RA susceptibility locus.

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References

  1. Seldin MF, Amos CI, Ward R, Gregersen PK . The genetics revolution and the assault on rheumatoid arthritis Arthritis Rheum 1999 42: 1071–1079

    Article  CAS  PubMed  Google Scholar 

  2. Gregersen P, Silver J, Winchester R . The shared epitope hypothesis: An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis Arthritis Rheum 1987 30: 1205–1213

    Article  CAS  PubMed  Google Scholar 

  3. Jawaheer D, Seldin MF, Amos CI et al. A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases Am J Hum Genet 2001 68: 927–936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cornelis F, Faure S, Martinez M et al. New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study Proc Natl Acad Sci USA 1998 95: 10746–10750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bali D, Gourley S, Kostyu DD et al. Genetic analysis of multiplex rheumatoid arthritis families Genes Immun 1999 1: 28–36

    Article  CAS  PubMed  Google Scholar 

  6. Shiozawa S, Hayashi S, Tsukamoto Y et al. Identification of the gene loci that predispose to rheumatoid arthritis Int Immunol 1998 10: 1891–1895

    Article  CAS  PubMed  Google Scholar 

  7. McDermott M, Kastner DL, Holloman JD et al. The role of T cell receptor beta chain genes in susceptibility to rheumatoid arthritis Arthritis Rheum 1995 38: 91–95

    Article  CAS  PubMed  Google Scholar 

  8. Barton A, Eyre S, Myerscough A et al. High resolution linkage and association mapping identifies a novel rheumatoid arthritis susceptibility locus homologous to one linked to two rat models of inflammatory arthritis Hum Mol Genet 2001 10: 1901–1906

    Article  CAS  PubMed  Google Scholar 

  9. Becker KG, Simon RM, Bailey-Wilson JE et al. Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases Proc Natl Acad Sci USA 1998 95: 9979–9984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wilder R, Remmers E, Kawahito Y, Gulko P, Cannon G, Griffiths M . Genetic factors regulating experimental arthritis in mice and rats In: Theophilopoulos A (ed) Current Directions in Autoimmunity: Genes and Genetics of Autoimmunity Vol. 1: Karger: Basel 1999 pp 121–165

    Chapter  Google Scholar 

  11. Gulko PS, Kawahito Y, Remmers EF et al. Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats Arthritis Rheum 1998 41: 2122–2131

    Article  CAS  PubMed  Google Scholar 

  12. Myerscough A, John S, Barrett JH, Ollier WE, Worthington J . Linkage of rheumatoid arthritis to insulin-dependent diabetes mellitus loci: evidence supporting a hypothesis for the existence of common autoimmune susceptibility loci Arthritis Rheum 2000 43: 2771–2775

    Article  CAS  PubMed  Google Scholar 

  13. Seki T, Selby J, Haupl T, Winchester R . Use of differential subtraction method to identify genes that characterize the phenotype of cultured rheumatoid arthritis synoviocytes Arthritis Rheum 1998 41: 1356–1364

    Article  CAS  PubMed  Google Scholar 

  14. Andress DL . Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor Am J Physiol 1998 274: E744–E750

    CAS  PubMed  Google Scholar 

  15. Ewton DZ, Coolican SA, Mohan S, Chernausek SD, Florini JR . Modulation of insulin-like growth factor actions in L6A1 myoblasts by insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5: a dual role for IGFBP-5 J Cell Physiol 1998 177: 47–57

    Article  CAS  PubMed  Google Scholar 

  16. Matsumoto T, Tsurumoto T, Goldring MB, Shindo H . Differential effects of IGF-binding proteins, IGFBP-3 and IGFBP-5, on IGF-I action and binding to cell membranes of immortalized human chondrocytes J Endocrinol 2000 166: 29–37

    Article  CAS  PubMed  Google Scholar 

  17. Morahan G, Huang D, Tait BD, Colman PG, Harrison LC . Markers on distal chromosome 2q linked to insulin-dependent diabetes mellitus Science 1996 272: 1811–1813

    Article  CAS  PubMed  Google Scholar 

  18. Fu J, Ikegami H, Kawaguchi Y et al. Association of distal chromosome 2q with IDDM in Japanese subjects Diabetologia 1998 41: 228–232

    Article  CAS  PubMed  Google Scholar 

  19. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis Arthritis Rheum 1988 31: 315–324

    Article  CAS  PubMed  Google Scholar 

  20. Chen Y, Winchester R, Korber B et al. Influence of HLA alleles on the rate of progression of vertically transmitted HIV infection in children: association of several HLA-DR13 alleles with long-term survivorship and the potential association of HLA-A*2301 with rapid progression to AIDS. Long-Term Survivor Study Hum Immunol 1997 55: 154–162

    Article  CAS  PubMed  Google Scholar 

  21. Hodge SE . The information contained in multiple sibling pairs Genet Epidemiol 1984 1: 109–122

    Article  CAS  PubMed  Google Scholar 

  22. Cottingham RW Jr, Idury RM, Schaffer AA . Faster sequential genetic linkage computations Am J Hum Genet 1993 53: 252–263

    PubMed  PubMed Central  Google Scholar 

  23. Schaffer AA, Gupta SK, Shriram K, Cottingham RW Jr . Avoiding recomputation in linkage analysis Hum Hered 1994 44: 225–237

    Article  CAS  PubMed  Google Scholar 

  24. Greenberg DA, Abreu P, Hodge SE . The power to detect linkage in complex disease by means of simple LOD-score analyses Am J Hum Genet 1998 63: 870–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hodge SE, Abreu PC, Greenberg DA . Magnitude of type I error when single-locus linkage analysis is maximized over models: a simulation study Am J Hum Genet 1997 60: 217–227

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Abreu PC, Greenberg DA, Hodge SE . Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases Am J Hum Genet 1999 65: 847–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ott J . Analysis of Human Genetic Linkage Johns Hopkins University Press: Baltimore 1991

    Google Scholar 

  28. Terwilliger JD, Goring HH . Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design Hum Biol 2000 72: 63–132

    CAS  PubMed  Google Scholar 

  29. Broman K . Estimation of allele frequencies with data on sibships Genet Epidemiol 2001 20: 307–315

    Article  CAS  PubMed  Google Scholar 

  30. Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results Nat Genet 1995 11: 241–247

    Article  CAS  PubMed  Google Scholar 

  31. Rozzo SJ, Allard JD, Choubey D et al. Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus Immunity 2001 15: 435–443

    Article  CAS  PubMed  Google Scholar 

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Author information

Author notes

  1. P S Gulko

    Present address: Center for Genomics and Human Genetics, North Shore-Long Island Jewish Research Institute, Manhasset, NY, USA

Authors and Affiliations

  1. New York Psychiatric Institute, New York, NY, USA

    S L Slager & S E Hodge

  2. Department of Psychiatry and Department of Biostatistics, Columbia University College of Physicians and Surgeons, New York, NY, USA

    S L Slager & S E Hodge

  3. Millenium Pharmaceuticals Inc, Cambridge, MA, USA

    L Carleu

  4. Division of Molecular Genetics, Columbia University College of Physicians and Surgeons, New York, NY, USA

    W K Chung

  5. Division of Autoimmune and Molecular Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA

    T Jackson, R J Winchester & P S Gulko

  6. Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    R J Winchester & P S Gulko

Authors
  1. S L Slager
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  2. L Carleu
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  3. W K Chung
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  4. T Jackson
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  5. R J Winchester
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  6. S E Hodge
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  7. P S Gulko
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Corresponding author

Correspondence to P S Gulko.

Additional information

This work was funded in part by National Institutes of Health grant DK-31813 from NIDDK to Dr S Hodge, and the Autoimmunity Centers of Excellence grant AI-46132 from NIAID to Drs P Gulko and R Winchester. The collection of clinical samples used in this research was funded by Millennium Pharmaceuticals Inc.

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Slager, S., Carleu, L., Chung, W. et al. The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid arthritis. Genes Immun 3, 110–113 (2002). https://doi.org/10.1038/sj.gene.6363847

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  • DOI: https://doi.org/10.1038/sj.gene.6363847

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