Skip to main content
SpringerLink
Log in

Genetic Factors in Type 1 Diabetes

  • Chapter
Genetics of Diabetes Mellitus

Part of the book series: Endocrine Updates ((ENDO,volume 10))

Abstract

Insulin-dependent diabetes mellitus (IDDM), or type 1 diabetes, is a chronic and yet incurable disease characterized by autoimmune destruction of pancreatic ß-cells and complete insulin deficiency (1). The disease develops predominantly in children or adolescents, but it can develop at a much later age, and it is quite heterogeneous in its clinical expression. A large body of evidence indicates that inherited genetic factors influence both susceptibility to and resistance from the disease. During the past few years, dramatic improvements in the ability to investigate the genetics of complex diseases have been introduced. The increasing availability of polymorphic microsatellite markers, automated typing technology (2), and large collections of families with affected sib-pairs have enabled the design of large scale, genome-wide scans to map IDDM susceptibility genes. Such scans have provided evidence to link diabetes susceptibility with numerous chromosomal regions and suggested that type 1 diabetes is a polygenic disorder. Moreover, there is evidence for epistatic phenomena involving several loci, and complex parental effects appear to influence susceptibility by modifying the transmission and expression of inherited genes.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Schranz, D.B. and A. Lernmark. 1998. Immunology in diabetes: An update. Diabetes-Metabolism Rev 14:3–29.

    Article  CAS  Google Scholar 

  2. Hearne, C.M. and J.A. Todd. 1992. Microsatellites for linkage analysis of genetic traits. Trends Genet 8:288–294.

    PubMed  CAS  Google Scholar 

  3. Johnson, A.H., C.K. Hurley, R.J. Hartzman, C.A. Alper, and E.J. Yunis. 1991. HLA: The major histocompatibility complex of man. In 18th edition Clinical Diagnosis & Management by Laboratory Methods. J.B. Henry, editor. WB Saunders, Philadelphia. 761–794.

    Google Scholar 

  4. Thomson, G., W.P. Robinson, M.K. Kuhner, S. Joe, M.J. MacDonald, J.L. Gottschall, J. Barbosa, S.S. Rich, J. Bertrams, M.P. Baur, J. Partanen, B.D. Tait, E. Schober, W.R. Mayr, J. Ludvigsson, B. Linblom, N.R. Farid, C. Thompson, and I. Deschamps. 1988. Genetic heterogeneity, modes of inheritance, and risk estimates; a joint study of caucasians with insulin-dependent diabetes mellitus. Am.J.Hum.Genet. 43:799–816.

    PubMed  CAS  Google Scholar 

  5. Todd, J.A., J.I. Bell, and H.O. McDevitt. 1987. HLA-DQ beta gene contribution to susceptibility and resistance to insulin dependent diabetes mellitus. Nature 329:599–604.

    Article  PubMed  CAS  Google Scholar 

  6. Horn, G.T., T.L. Bugawan, C.M. Long, and H.A. Erlich. 1988. Allelic sequence variation of the HLA-DQ loci: Relationship to serology and to insulin-dependent diabetes mellitus susceptibility. Proc Nall Acad Sci USA 85:6012–6016.

    Article  CAS  Google Scholar 

  7. Baisch, J.M., T. Week, R. Giles, M. Hoover, P. Stastny, and D. Capra. 1990. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. N Eng J Med 322:1836–1841.

    Article  CAS  Google Scholar 

  8. Pugliese, A., R. Gianani, R. Moromisato, Z.L. Awdeh, C.A. Alper, H.A. Erlich, R.A. Jackson, and G.S. Eisenbarth. 1995. HLA-DQB 1 *0602 is associated with dominant protection from diabetes even among islet cell antibody-positive first-degree relatives of patients with IDDM. Diabetes 44:608–613.

    Article  PubMed  CAS  Google Scholar 

  9. Pugliese, A., E. Kawasaki, M. Zeller, L. Yu, S. Babu, M. Solimena, C.T. Moraes, M. Pietropaolo, R.P. Friday, M. Trucco, C. Ricordi, M. Allen, J.A. Noble, H.A. Erlich, and G.S. Eisenbarth. 1999. Sequence analysis of the diabetes-protective human leukocyte antigen- DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes. J.Clin.Endocrinol.Metab. 84:1722–1728.

    Article  PubMed  CAS  Google Scholar 

  10. Bell, G.I., S. Horita, and J.H. Karam. 1984. A polymorphic locus near the human insulin gene is associated with insulin dependent diabetes mellitus. Diabetes 33:176–183.

    Article  PubMed  CAS  Google Scholar 

  11. Julier, C., R.N. Hyer, J. Davies, F. Merlin, P. Soularue, L. Briant, G. Cathelineau, I. Deschamps, J.I. Rotter, P. Froguel, C. Boitard, J.I. Bell, and G.M. Lathrop. 1991. Insulin-IGF2 region encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354:155–159.

    Article  PubMed  CAS  Google Scholar 

  12. Lucassen, A., C. Julier, J.-P. Beressi, C. Boitard, P. Froguel, M. Lathrop, and J.I. Bell. 1993. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genetics 4:305–310.

    Article  CAS  Google Scholar 

  13. Owerbach, D. and K.H. Gabbay. 1993. Localization of a Type I diabetes susceptibility locus to the variable tandem repeat region flanking the insulin gene. Diabetes 42:1708–1714.

    Google Scholar 

  14. Pugliese, A., Z.L. Awdeh, C.A. Alper, R.A. Jackson, and G.S. Eisenbarth. 1994. The paternally inherited insulin gene B allele (1,428 FokI site) confers protection from insulin-dependent diabetes in families. Journal ofAutoimmunity 7:687–694.

    Article  CAS  Google Scholar 

  15. Bennett, S.T., A.M. Lucassen, S.C.L. Gough, E.E. Powell, D.E. Undlien, L.E. Pritchard, M.E. Merriman, Y. Kawaguchi, M.J. Dronsfield, F. Pociot, J. Nerup, N. Bouzekri, A. Cambot-Thomsen, K.S. Ronningen, A.H. Barnett, S.C. Bain, and J.A. Todd. 1995. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nature Genetics 9:284–292.

    Article  PubMed  CAS  Google Scholar 

  16. Undlien, D.E., S.T. Bennett, J.A. Todd, H.E. Akselsen, I. Ikaheimo, H. Reijonen, M. Knip, E. Thorsby, and K.S. Ronningen. 1995. Insulin gene region-encoded susceptibility to IDDM maps upstream of the insulin gene. Diabetes 44:620–625.

    Article  PubMed  CAS  Google Scholar 

  17. Julier, C., A. Lucassen, P. Villedieu, M. Delepine, C. Levy-Marchal, P.M. Danze, F. Bianchi, C. Boitard, P. Froguel, J. Bell, and G.M. Lathrop. 1994. Multiple DNA variant association analysis: application to the insulin gene region in type I diabetes. Am.J.Hum.Genet. 55:1247–1254.

    PubMed  CAS  Google Scholar 

  18. Pugliese, A., M. Zeller, A.J. Fernandez, L.J. Zalcberg, R.J. Bartlett, C. Ricordi, M. Pietropaolo, G.S. Eisenbarth, S.T. Bennett, and D.D. Patel. 1997. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat.Genet. 15:293–297.

    Google Scholar 

  19. Vafiadis, P., S.T. Bennett, J.A. Todd, J. Nadeau, R. Grabs, C.G. Goodyear, S. Wickramasinghe, E. Colle, and C. Polychronakos. 1997. Insulin expression in the thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nature Genetics 15:289–292.

    Article  PubMed  CAS  Google Scholar 

  20. Field, L.L., R. Tobias, and T. Magnus. 1994. A locus on chromosome 15q26 (IDDM3) produces susceptibility to insulin-dependent diabetes mellitus [see comments]. Nat. Genet. 8:189–194.

    Article  PubMed  CAS  Google Scholar 

  21. Luo, D.F., M.M. Bui, A. Muir, N.K. Maclaren, G. Thomson, and J.X. She. 1995. Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27. Am.J.Hum.Genet. 57:911–919.

    PubMed  CAS  Google Scholar 

  22. Zamani, M., F. Pociot, P. Raeymaekers, J. Nerup, and J.J. Cassiman. 1996. Linkage of type 1 diabetes to 15q26 (IDDM3) in the Danish population. Hum.Genet. 98:491–496.

    Article  PubMed  CAS  Google Scholar 

  23. Luo, D.F., R. Buzzetti, J.I. Rotter, N.K. Maclaren, L.J. Raffel, L. Nistico, C. Giovannini, P. Pozzilli, G. Thomson, and J.X. She. 1996. Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum.Mol.Genet. 5:693–698.

    Article  PubMed  CAS  Google Scholar 

  24. Davies, J.L., Y. Kawaguchi, S.T. Bennett, J.B. Copeman, H.J. Cordell, L.E. Pritchard, P.W. Reed, S.C. Gough, S.C. Jenkins, and S.M. Palmer. 1994. A genome-wide search for human type 1 diabetes susceptibility genes [see comments]. Nature 371:130–136.

    Article  PubMed  CAS  Google Scholar 

  25. Hashimoto, L., C. Habita, J.P. Beressi, M. Delepine, C. Besse, A. Cambon-Thomsen, I. Deschamps, J.I. Rotter, S. Djoulah, M.R. James, P. Froguel, J. Weissenbach, G.M. Lathrop, and C. Julier. 1994. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome l lq. Nature 371:161–164.

    Article  PubMed  CAS  Google Scholar 

  26. Cordell, H.J., J.A. Todd, S.T. Bennett, Y. Kawaguchi, and M. Farrall. 1995. Two-locus maximum lod score analysis of a multifactorial trait: joint consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes. Am.J.Hum.Genet. 57:920–934.

    PubMed  CAS  Google Scholar 

  27. Buhler, J., D. Owerbach, A.A. Schaffer, M. Kimmel, and K.H. Gabbay. 1997. Linkage analyses in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases. Hum.Hered. 47:211–222.

    Article  PubMed  CAS  Google Scholar 

  28. Pritchard, L.E., Y. Kawaguchi, P.W. Reed, J.B. Copeman, J.L. Davies, A.H. Bamett, S.C. Bain, and J.A. Todd. 1995. Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping. Hum.Mol.Genet. 4:197–202.

    Article  PubMed  CAS  Google Scholar 

  29. Wong, S., S. Moore, S. Orisio, A. Millward, and A.G. Demaine. 1991. Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11. Cl in. exp. Imm uno 1. 83:69–73.

    Google Scholar 

  30. Hey, P.J., R.C. Twells, M.S. Phillips, N. Yusuke, S.D. Brown, Y. Kawaguchi, R. Cox, X. Guochun, V. Dugan, H. Hammond, M.L. Metzker, J.A. Todd, and J.F. Hess. 1998. Cloning of a novel member of the low-density lipoprotein receptor family. Gene 216:103–111.

    Article  PubMed  CAS  Google Scholar 

  31. Kim, P.K., A.S. Dutra, S.C. Chandrasekharappa, and J.M. Puck. 1996. Genomic structure and mapping of human FADD, an intracellular mediator of lymphocyte apoptosis. J.Immunol. 157:5461–5466.

    PubMed  CAS  Google Scholar 

  32. Chervonsky, A.V., Y. Wang, F.S. Wong, I. Visintin, R.A. Flavell, C.A.J. Janeway, and L.A. Matis. 1997. The role of Fas in autoimmune diabetes. Cell 89:17–24.

    Article  PubMed  CAS  Google Scholar 

  33. Stassi, G., R.D. Maria, G. Trueco, W. Rudert, R. Testi, A. Galluzzo, C. Giordano, and M. Trueco. 1997. Nitric oxide primes pancreatic beta cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J.Exp.Med. 186:1193–1200.

    Article  PubMed  CAS  Google Scholar 

  34. Nakagawa, Y., Y. Kawaguchi, R.C. Twells, C. Muxworthy, K.M. Hunter, A. Wilson, M.E. Merriman, R.D. Cox, T. Merriman, F. Cucca, P.A. McKinney, J.P. Shield, J. Tuomilehto, E. Tuomilehto-Wolf, C. lonesco-Tirgoviste, Nistic, R. Buzzetti, P. Pozzilli, F. San-Raffaele, G. Joner, E. Thorsby, D.E. Undlien, F. Pociot, J. Nerup, K.S. nningen, F.S.G. Bart’s-Oxford, S.C. Bain, J.A. Todd, and IDDM4. 1998. Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11g13. Am.J.Hum.Genet. 63:547–556.

    Google Scholar 

  35. Davies, J.L., F. Cucca, J.V. Goy, Z.A. Atta, M.E. Merriman, A. Wilson, A.H. Barnett, S.C. Bain, and J.A. Todd. 1996. Saturation multipoint linkage mapping of chromosome 6q in type 1 diabetes. Hum.Mol.Genet. 5:1071–1074.

    Article  PubMed  CAS  Google Scholar 

  36. Delepine, M., F. Pociot, C. Habita, L. Hashimoto, P. Froguel, J. Rotter, A. Cambon-Thomsen, I. Deschamps, S. Djoulah, J. Weissenbach, J. Nerup, M. Lathrop, and C. Julier. 1997. Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am.J.Hum.Genet. 60:174–187.

    PubMed  CAS  Google Scholar 

  37. Hodge, S.E., C.E. Anderson, K. Neiswanger, L.L. Field, M.A. Spence, R.S. Sparkes, M. Christ, P.I. Terasaki, D.L. Rimoin, and J.I. Rotter. 1982. Close genetic linkage between diabetes mellitus and Kidd Blood group. Lancet ii:893

    Google Scholar 

  38. Merriman, T., R. Twells, M. Merriman, I. Eaves, R. Cox, F. Cucca, P. McKinney, J. Shield, D. Baum, E. Bosi, P. Pozzilli, L. Nistico, R. Buzzetti, G. Joner, K. Ronningen, E. Thorsby, D. Undlien, F. Pociot, J. Nerup, S. Bain, A. Barnett, and J. Todd. 1997. Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18g21. Hum.Mol.Genet. 6:1003–1010.

    Article  PubMed  CAS  Google Scholar 

  39. Merriman, T.R., I.A. Eaves, R.C. Twells, M.E. Merriman, P.A. Danoy, C.E. Muxworthy, K.M. Hunter, R.D. Cox, F. Cucca, P.A. McKinney, J.P. Shield, J.D. Baum, J. Tuomilehto, E. Tuomilehto-Wolf, C. Ionesco-Tirgoviste, G. Joner, E. Thorsby, D.E. Undlien, F. Pociot, J. Nerup, K.S. Ronningen, S.C. Bain, and J.A. Todd. 1998. Transmission of haplotypes of microsatellite markers rather than single marker alleles in the mapping of a putative type 1 diabetes susceptibility gene (IDDM6). Hum.Mol.Genet. 7:517–524.

    Article  PubMed  CAS  Google Scholar 

  40. Holmes, D.I., N.A. Wahab, and R.M. Mason. 1999. Cloning and characterization of ZNF236, a glucose-regulated Kruppel-like zinc-finger gene mapping to human chromosome 18q22-q23. Genomics 60:105–109.

    Article  PubMed  CAS  Google Scholar 

  41. Copeman, J.B., F. Cucca, C.M. Hearne, R.J. Cornall, P.W. Reed, K.S. Ronningen, D.E. Undlien, L. Nistico, R. Buzzetti, and R. Tosi. 1995. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2g31-q33. Nat.Genet. 9:8085.

    Article  Google Scholar 

  42. Esposito, L., N.J. Hill, L.E. Pritchard, F. Cucca, C. Muxworthy, M.E. Merriman, A. Wilson, C. Julier, M. Delepine, J. Tuomilehto, E. Tuomilehto-Wolf, C. Ionesco-Tirgoviste, L. Nistico’, R. Buzzetti, P. Pozzilli, M. Ferrari, E. Bosi, F. Pociot, J. Nerup, S.C. Bain, and J.A. Todd. 1998. Genetic analysis of chromosome 2 in type 1 diabetes: analysis of putative loci IDDM7, IDDM12, and IDDM13 and candidate genes NRAMP1 and IA-2 and the interleukin-1 gene cluster. IMDIAB Group [In Process Citation]. Diabetes 47:1797–1799.

    Article  PubMed  CAS  Google Scholar 

  43. Luo, D.F., N.K. Maclaren, H.S. Huang, A. Muir, and J.X. She. 1995. Intrafamilial and case-control association analysis of D2S 152 in insulin-dependent diabetes. Autoimmunity. 21:143–147.

    Article  PubMed  CAS  Google Scholar 

  44. Kristiansen, O.P., F. Pociot, E.P. Bennett, H. Clausen, J. Johannesen, J. Nerup, and T. Mandrup-Poulsen. IDDM7 links to insulin-dependent diabetes mellitus in Danish multiplex families but linkage is not explained by novel polymorphisms in the candidate gene GALNT3. The Danish Study Group of Diabetes in Childhood and The Danish IDDM Epidemiology and Genetics Group. Hum.Mutat.(Online.) 2000.Mar.;15.(3.):295.-6. 15:295–296.

    Google Scholar 

  45. Owerbach, D. and Gabbay, K. H. 1995. The HOXD8 locus (2q31) is linked to type I diabetes. Interaction with chromosome 6 and 11 disease susceptibility genes. Diabetes 44, 132–136.

    Article  PubMed  CAS  Google Scholar 

  46. Tamimi, R., E. Steingrimsson, N.G. Copeland, K. Dyer-Montgomery, J.E. Lee, R. Hernandez, N.A. Jenkins, and S.J. Tapscott. 1996. The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2. Genomics 34:418–421.

    Article  PubMed  CAS  Google Scholar 

  47. Iwata, I., S. Nagafuchi, H. Nakashima, S. Kondo, T. Koga, Y. Yokogawa, T. Akashi, T. Shibuya, Y. Umeno, T. Okeda, S. Shibata, S. Kono, M. Yasunami, H. Ohkubo, and Y. Niho. 1999. Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese. Diabetes 48:416–419.

    Article  PubMed  CAS  Google Scholar 

  48. Dupont, S., C. Dina, E.H. Hani, and P. Froguel. 1999. Absence of replication in the French population of the association between beta 2/NEUROD-A45T polymorphism and type 1 diabetes. Diabetes Metab. 25:516–517.

    PubMed  CAS  Google Scholar 

  49. Bennett, E.P., H. Hassan, U. Mandel, M.A. Hollingsworth, N. Akisawa, Y. Ikematsu, G. Merkx, A.G. van Kessel, S. Olofsson, and H. Clausen. 1999. Cloning and characterization of a close homologue of human UDP-N-acetyl-alpha-Dgalactosamine:Polypeptide N-acetylgalactosaminyltransferase-T3, designated GaINAc-T6. Evidence for genetic but not functional redundancy. J.Biol.Chem. 274:25362–25370.

    Article  PubMed  CAS  Google Scholar 

  50. Delepine, M., F. Pociot, C. Habita, L. Hashimoto, P. Froguel, J. Rotter, A. Cambon-Thomsen, I. Deschamps, S. Djoulah, J. Weissenbach, J. Nerup, M. Lathrop, and C. Julier. 1997. Evidence for a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am.J.Hum.Genet. 60:174–187.

    PubMed  CAS  Google Scholar 

  51. Paterson, A.D., P. Rahman, and A. Petronis. 1999. IDDM9 and a locus for rheumatoid arthritis on chromosome 3q appear to be distinct. Hum.Immunol. 60:883–885.

    Article  PubMed  CAS  Google Scholar 

  52. Reed, P., F. Cucca, S. Jenkins, M. Merriman, A. Wilson, P. McKinney, E. Bosi, G. Joner, K. Ronningen, E. Thorsby, D. Undlien, T. Merriman, A. Barnett, S. Bain, and J. Todd. 1997. Evidence for a type 1 diabetes susceptibility locus (IDDM10) on human chromosome 10p11-q11. Hum.Mol.Genet. 6:1011–1016.

    Article  PubMed  CAS  Google Scholar 

  53. Field, L.L., R. Tobias, G. Thomson, and S. Plon. 1996. Susceptibility to insulin-dependent diabetes mellitus maps to a locus (IDDM11) on human chromosome 14g24.3-q31. Genomics 33:1–8.

    Article  PubMed  CAS  Google Scholar 

  54. Heron, L., A. Virsolvy, F. Apiou, A. Le Cam, and D. Bataille. 1999. Isolation, characterization, and chromosomal localization of the human ENSA gene that encodes alpha-endosulfine, a regulator of beta-cell K(ATP) channels. Diabetes 48:1873–1876.

    Article  PubMed  CAS  Google Scholar 

  55. Harada, Y., K. Ozaki, M. Suzuki, T. Fujiwara, E. Takahashi, Y. Nakamura, and A. Tanigami. 1999. Complete cDNA sequence and genomic organization of a human pancreas-specific gene homologous to Caenorhabditis elegans se1–1. J.Hum.Genet. 44:330–336.

    Article  PubMed  CAS  Google Scholar 

  56. Apelqvist, A., H. Li, L. Sommer, P. Beatus, D.J. Anderson, T. Honjo, d.A. Hrabe, U. Lendahl, and H. Edlund. 1999. Notch signalling controls pancreatic cell differentiation. Nature 400:877–881.

    Article  PubMed  CAS  Google Scholar 

  57. Nistico, L., R. Buzzetti, L.E. Pritchard, B. Van der Auwera, C. Giovannini, E. Bosi, M.T. Larrad, M.S. Rios, C.C. Chow, C.S. Cockram, K. Jacobs, C. Mijovic, S.C. Bain, A.H. Barnett, C.L. Vandewalle, F. Schuit, F.K. Gorus, R. Tosi, P. Pozzilli, and J.A. Todd. 1996. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. Hum.Mol.Genet. 5:1075-1080.

    Article  PubMed  CAS  Google Scholar 

  58. Marron, M.P., L.J. Raffel, H.J. Garchon, C.O. Jacob, M. Serrano-Rios, L.M. Martinez, W.P. Teng, Y. Park, Z.X. Zhang, D.R. Goldstein, Y.W. Tao, G. Beaurain, J.F. Bach, H.S. Huang, D.F. Luo, A. Zeidler, J.I. Rotter, M.C. Yang, T. Modilevsky, N.K. Maclaren, and J.X. She. 1997. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Hum.Mol.Genet. 6:1275–1282.

    Article  PubMed  CAS  Google Scholar 

  59. Awata, T., S. Kurihara, M. Iitaka, S. Takei, I. Inoue, C. Ishii, K. Negishi, T. Izumida, Y. Yoshida, R. Hagura, N. Kuzuya, Y. Kanazawa, and S. Katayama. 1998. Association of CTLA-4 gene A-G polymorphism (IDDM 12 locus) with acute-onset and insulin-depleted IDDM as well as autoimmune thyroid disease (Graves’ disease and Hashimoto’s thyroiditis) in the Japanese population. Diabetes 47:128–129.

    PubMed  CAS  Google Scholar 

  60. Hayashi, H., I. Kusaka, S. Nagasaka, A. Kawakami, K. Rokkaku, T. Nakamura, T. Saito, M. Higashiyama, K. Honda, and S.E. lshikawa. 1999. Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus. Clin.Endocrinol.(Oxf.) 51:793–799.

    Article  CAS  Google Scholar 

  61. Yanagawa, T., T. Maruyama, K. Gomi, M. Taniyama, A. Kasuga, Y. Ozawa, M. Terauchi, H. Hirose, H. Maruyama, and T. Saruta. 1999. Lack of association between CTLA-4 gene polymorphism and IDDM in Japanese subjects. Autoimmunity. 29:53–56.

    Article  PubMed  CAS  Google Scholar 

  62. Larsen, Z.M., O.P. Kristiansen, E. Mato, J. Johannesen, M. Puig-Domingo, A. de Leiva, J. Nerup, and F. Pociot. 1999. IDDM12 (CTLA4) on 2q33 and IDDM13 on 2q34 in genetic susceptibility to type 1 diabetes (insulin-dependent). Autoimmunity. 31:35–42.

    Article  PubMed  CAS  Google Scholar 

  63. Badenhoop, K., H. Donner, M. Pani, H. Rau, T. Siegmund, and J. Braun. 1999. Genetic susceptibility to type I diabetes: clinical and molecular heterogeneity of IDDMI and IDDM12 in a german population. Exp.Clin.Endocrinol.Diabetes 107 Suppl 3:S8992:S89–S92

    Article  Google Scholar 

  64. Morahan, G., D. Huang, B.D. Tait, P.G. Colman, and L.C. Harrison. 1996. Markers on distal chromosome 2q linked to insulin-dependent diabetes mellitus. Science 272:1811–1813.

    Google Scholar 

  65. Fu, J., H. Ikegami, Y. Kawaguchi, T. Fujisawa, Y. Kawabata, Y. Hamada, H. Ueda, M. Shintani, K. Nojima, N. Babaya, Q.J. Shen, Y. Uchigata, T. Urakami, Y. Omori, K. Shima, and T. Ogihara. 1998. Association of distal chromosome 2q with IDDM in Japanese subjects. Diabetologia 41:228–232.

    Article  PubMed  CAS  Google Scholar 

  66. Giannini, S., S. Mohan, J. Kasuya, G. Galli, C.M. Rotella, T.R. LeBon, and Y. FujitaYamaguichi. 1994. Characterization of insulin-like growth factor-binding proteins produced by cultured fibroblasts from patients with noninsulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, or obesity. J. CIin.Endocrinol.Metab. 79:1824–1830.

    Article  CAS  Google Scholar 

  67. Owerbach, D., F.J. Naya, M.J. Tsai, S.V. Allander, D.R. Powell, and K.H. Gabbay. 1997. Analysis of candidate genes for susceptibility to type I diabetes: a case-control and family-association study of genes on chromosome 2g31–35. Diabetes 46:1069–1074.

    Article  PubMed  CAS  Google Scholar 

  68. Temple, I.K., R.S. James, J.A. Crolla, F.L. Sitch, P.A. Jacobs, W.M. Howell, P. Betts, J.D. Baum, and J.P.H. Shield. 1995. An imprinted gene(s) for diabetes? Nat Genet 9:110–112.

    Google Scholar 

  69. . Haig, D. 1995. Is human insulin imprinted? Nat Genet 7:10

    Article  Google Scholar 

  70. Verge, C.F., P. Vardi, S. Babu, F. Bao, H.A. Erlich, T. Bugawan, D. Tiosano, L. Yu, G.S. Eisenbarth, and P.R. Fain. 1998. Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family. J.Clin.Invest. 102:1569–1575.

    Article  PubMed  CAS  Google Scholar 

  71. Rowe, R.E., B. Wapelhorst, G.I. Bell, N. Risch, R.S. Spielman, and P. Concannon. 1995. Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7. Nat. Genet. 10:240–242.

    Article  PubMed  CAS  Google Scholar 

  72. Concannon, P., K.J. Gogolin-Ewens, D.A. Hinds, B. Wapelhorst, V.A. Morrison, B. Stirling, M. Mitra, J. Farmer, S.R. Williams, N.J. Cox, G.I. Bell, N. Risch, and R.S. Spielman. 1998. A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus [see comments]. Nat.Genet. 19:292–296.

    Article  PubMed  CAS  Google Scholar 

  73. Cucca, F., J.V. Goy, Y. Kawaguchi, L. Esposito, M.E. Merriman, A.J. Wilson, H.J. ordell, S.C. in, and J.A. odd. 1998. A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients. Nat Genet 19:301–302.

    CAS  Google Scholar 

  74. Warram, J.H., A.S. Krolewski, M.S. Gottlieb, and C.R. Kahn. 1984. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. New England Journal of Medicine 311, No.3:149–152.

    Article  PubMed  CAS  Google Scholar 

  75. Warram, J.H., C.M. Blaise, and A.S. Krolewski. 1991. Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy. Diabetes 40:1679–1684.

    Google Scholar 

  76. Bleich, D., M. Polak, G.S. Eisenbarth, and R.A. Jackson. 1993. Decreased risk of type I diabetes in offspring of mothers who acquire diabetes during adrenarchy. Diabetes 42:1433–1439.

    Article  PubMed  CAS  Google Scholar 

  77. Vadheim, C.M., J.I. Rotter, N.K. Maclaren, W.J. Riley, and C.E. Anderson. 1986. Preferential transmission of diabetic alleles within the HLA gene complex. New England Journal of Medicine 315:1314–1318.

    Article  PubMed  CAS  Google Scholar 

  78. Deschamps, I., J. Hors, F. Clerget-Darpoux, E. Gardais, J.J. Robert, A. Marcelli-Berge, H. Lestradet, and J. Dausset. 1990. Excess of maternal HLA-DR3 antigens in HLA DR3,4 positive type 1 (insulin-dependent) diabetic patients. Diabetologia 33:425–439.

    Article  PubMed  CAS  Google Scholar 

  79. Bain, S.C., B.R. Rowe, and A.H.T.J.A. Barnett. 1994. Parental origin of diabetes-associated HLA types in sibling pairs with type I diabetes. Diabetes 43:1462–1468.

    Article  PubMed  CAS  Google Scholar 

  80. Bui, M.M., D.-F. Luo, J.Y. She, N.K. Maclaren, A. Muir, G. Thomson, and J.-X. She. 1996. Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas. Journal ofAutoimmunity 9:97–103.

    Article  CAS  Google Scholar 

  81. Polychronakos, C., A. Kukuvitis, N. Giannoukakis, and E. Colle. 1995. Parental Imprinting effect at the INS-IGF2 diabetes susceptibility locus. Diabetologia 38:715–719.

    Google Scholar 

  82. Bennett, S.T., A.J. Wilson, F. Cucca, J. Nerup, F. Pociot, P.A. McKinney, A.H. Barnett, S.C. Bain, and J.A. Todd. 1996. IDDM2-VNTR-encoded susceptibility to type 1 diabetes: dominant protection and parental transmission of alleles of the insulin gene-linked minisatellite locus. Journal of Autoimmunity 9:415–421.

    Article  PubMed  CAS  Google Scholar 

  83. . Hoffman, A.R. and T.H. Vu. 1996. Genomic Imprinting. Scientific American 1:52-61.

    Google Scholar 

  84. Akerblom, H.K. and M. Knip. 1998. Putative environmental factors in Type 1 Diabetes. Diabetes-Metabolism Reviews 14:31–67.

    PubMed  CAS  Google Scholar 

  85. Conrad, B., R.N. Weissmahr, J. Boni, R. Arcari, J. Schupbach, and B. Mach. 1997. A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes. Cell 90:303–313.

    Article  PubMed  CAS  Google Scholar 

  86. Conrad, B., E. Weldmann, G. Trueco, W.A. Rudert, R. Behboo, C. Ricordi, H. RodriquezRilo, D. Finegold, and M. Trueco. 1994. Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 371:351–355.

    Article  PubMed  CAS  Google Scholar 

  87. Knerr, I., R. Repp, J. Dotsch, N. Gratzki, J. Hanze, T. Kapellen, and W. Rascher. 1999. Quantitation of gene expression by real-time PCR disproves a “retroviral hypothesis” for childhood-onset diabetes mellitus. Pediatr.Res. 46:57–60.

    Article  PubMed  CAS  Google Scholar 

  88. Kim, A., H.S. Jun, L. Wong, D. Stephure, D. Pacaud, R.A. Trussell, and J.W. Yoon. 1999. Human endogenous retrovirus with a high genomic sequence homology with IDDMK(1,2)22 is not specific for Type I (insulin-dependent) diabetic patients but ubiquitous. Diabetologia 42:413–418.

    Article  PubMed  CAS  Google Scholar 

  89. Jaeckel, E., S. Heringlake, D. Berger, G. Brabant, G. Hunsmann, and M.P. Manns. 1999. No evidence for association between IDDMK(1,2)22, a novel isolated retrovirus, and IDDM. Diabetes 48:209–214.

    Article  PubMed  CAS  Google Scholar 

  90. Murphy, V.J., L.C. Harrison, W.A. Rudert, P. Luppi, M. Trucco, A. Fierabracci, P.A. Biro, and G.F. Bottazzo. 1998. Retroviral superantigens and type 1 diabetes mellitus. Cell 95:9–11.

    Article  PubMed  CAS  Google Scholar 

  91. Kim, A., H.S. Jun, L. Wong, D. Stephure, D. Pacaud, R.A. Trussell, and J.W. Yoon. 1999. Human endogenous retrovirus with a high genomic sequence homology with IDDMK(1,2)22 is not specific for Type I (insulin-dependent) diabetic patients but ubiquitous. Diabetologia 42:413–418.

    Article  PubMed  CAS  Google Scholar 

  92. Muir, A., Q.G. Ruan, M.P. Marron, and J.X. She. 1999. The IDDMK(1,2)22 retrovirus is not detectable in either mRNA or genomic DNA from patients with type 1 diabetes. Diabetes 48:219–222.

    Article  PubMed  CAS  Google Scholar 

  93. Badenhoop, K., H. Donner, J. Neumann, J. Herwig, R. Kurth, K.H. Usadel, and R.R. Tonjes. 1999. IDDM patients neither show humoral reactivities against endogenous retroviral envelope protein nor do they differ in retroviral mRNA expression from healthy relatives or normal individuals. Diabetes 48:215–218.

    Article  PubMed  CAS  Google Scholar 

  94. Lan, M.S., A. Mason, R. Coutant, Q.Y. Chen, A. Vargas, J. Rao, R. Gomez, S. Chalew, R. Garry, and N.K. Maclaren. 1998. HERV-KlOs and immune-mediated (type 1) diabetes. Cell 95:14–16.

    Article  PubMed  CAS  Google Scholar 

  95. Lower, R., R.R. Tonjes, K. Boller, J. Denner, B. Kaiser, R.C. Phelps, J. Lower, R. Kurth, K. Badenhoop, H. Donner, K.H. Usadel, T. Miethke, M. Lapatschek, and H. Wagner. 1998. Development of insulin-dependent diabetes mellitus does not depend on specific expression of the human endogenous retrovirus HERV-K. Cell 95:11–14.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Miami School of Medicine, Miami, FL, 33134, USA

    Alberto Pugliese M.D.

Authors
  1. Alberto Pugliese M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Northwestern University Medical School, Chicago, Illinois, USA

    William L. Lowe Jr. M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pugliese, A. (2001). Genetic Factors in Type 1 Diabetes. In: Lowe, W.L. (eds) Genetics of Diabetes Mellitus. Endocrine Updates, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1597-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1597-5_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5633-2

  • Online ISBN: 978-1-4615-1597-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation