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. 1990 Dec;82(3):538–541. doi: 10.1111/j.1365-2249.1990.tb05486.x

A T cell receptor beta chain polymorphism is associated with patients developing insulin-dependent diabetes after the age of 20 years.

S A McMillan 1, C A Graham 1, P J Hart 1, D R Hadden 1, T A McNeill 1
PMCID: PMC1535501  PMID: 1979939

Abstract

We have studied the BglII polymorphism near the T cell receptor beta chain constant region (TcR-C beta) gene, HLA-DR genotypes and certain autoimmune features in 102 patients with type I (insulin-dependent) diabetes. There was a significant decrease in the frequency of the 1:1 genotype (P = 0.008) and an increase in the 1:2 genotype (P = 0.03) of the BglII TcR polymorphism in the group of patients who developed type-I diabetes after the age of 20 years. This group of patients also showed an increased incidence of autoantibodies (especially islet cell antibody), a family history of diabetes and the presence of other autoimmune diseases. The frequency of this polymorphism in patients who developed type I diabetes before the age of 20 years was similar to a non-diabetic group. These results suggest that there are two genetically distinct groups of patients with type I diabetes. HLA-DR3 and HLA-DR4 genotypes were also increased in the diabetic patients but no significant difference was observed between HLA-DR genotypes, the TcR-C beta genotypes, the age of diagnosis or with other autoimmune features. Patients developing type I (insulin-dependent) diabetes after the age of 20 years have an additional genetic susceptibility for diabetes associated with the TcR-C beta gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bottazzo G. F., Cudworth A. G., Moul D. J., Doniach D., Festenstein H. Evidence for a primary autoimmune type of diabetes mellitus. Br Med J. 1978 Nov 4;2(6147):1253–1255. doi: 10.1136/bmj.2.6147.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Demaine A. G., Ratanachaiyavong S., Pope R., Ewins D., Millward B. A., McGregor A. M. Thyroglobulin antibodies in Graves' disease are associated with T-cell receptor beta chain and major histocompatibility complex loci. Clin Exp Immunol. 1989 Jul;77(1):21–24. [PMC free article] [PubMed] [Google Scholar]
  3. Field L. L., Anderson C. E., Neiswanger K., Hodge S. E., Spence M. A., Rotter J. I. Interaction of HLA and immunoglobulin antigens in type 1 (insulin-dependent) diabetes. Diabetologia. 1984 Nov;27(5):504–508. doi: 10.1007/BF00290384. [DOI] [PubMed] [Google Scholar]
  4. Hitman G. A., Tarn A. C., Winter R. M., Drummond V., Williams L. G., Jowett N. I., Bottazzo G. F., Galton D. J. Type 1 (insulin-dependent) diabetes and a highly variable locus close to the insulin gene on chromosome 11. Diabetologia. 1985 Apr;28(4):218–222. doi: 10.1007/BF00282236. [DOI] [PubMed] [Google Scholar]
  5. Hoover M. L., Capra J. D. The T cell receptor and autoimmune diseases. Mol Biol Med. 1987 Jun;4(3):123–132. [PubMed] [Google Scholar]
  6. Karjalainen J., Salmela P., Ilonen J., Surcel H. M., Knip M. A comparison of childhood and adult type I diabetes mellitus. N Engl J Med. 1989 Apr 6;320(14):881–886. doi: 10.1056/NEJM198904063201401. [DOI] [PubMed] [Google Scholar]
  7. Krolewski A. S., Warram J. H., Rand L. I., Kahn C. R. Epidemiologic approach to the etiology of type I diabetes mellitus and its complications. N Engl J Med. 1987 Nov 26;317(22):1390–1398. doi: 10.1056/NEJM198711263172206. [DOI] [PubMed] [Google Scholar]
  8. McMillan S. A., Hill A. J., Graham C. A., Nevin N. C., Fay A. C. T cell receptor beta chain polymorphisms are associated with cystic fibrosis. J Med Genet. 1989 Jul;26(7):431–433. doi: 10.1136/jmg.26.7.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Millward B. A., Welsh K. I., Leslie R. D., Pyke D. A., Demaine A. G. T cell receptor beta chain polymorphisms are associated with insulin-dependent diabetes. Clin Exp Immunol. 1987 Oct;70(1):152–157. [PMC free article] [PubMed] [Google Scholar]
  10. Robinson M. A., Kindt T. J. Segregation of polymorphic T-cell receptor genes in human families. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3804–3808. doi: 10.1073/pnas.82.11.3804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rotter J. I., Rimoin D. L. Heterogeneity in diabetes mellitus--update, 1978. Evidence for further genetic heterogeneity within juvenile-onset insulin-dependent diabetes mellitus. Diabetes. 1978 May;27(5):599–605. doi: 10.2337/diab.27.5.599. [DOI] [PubMed] [Google Scholar]
  12. Shoenfeld Y., Isenberg D. A. The mosaic of autoimmunity. Immunol Today. 1989 Apr;10(4):123–126. doi: 10.1016/0167-5699(89)90245-4. [DOI] [PubMed] [Google Scholar]
  13. Sims J. E., Tunnacliffe A., Smith W. J., Rabbitts T. H. Complexity of human T-cell antigen receptor beta-chain constant- and variable-region genes. Nature. 1984 Dec 6;312(5994):541–545. doi: 10.1038/312541a0. [DOI] [PubMed] [Google Scholar]
  14. Svejgaard A., Jakobsen B. K., Platz P., Ryder L. P., Nerup J., Christy M., Borch-Johnsen K., Parving H. H., Deckert T., Mølsted-Pedersen L. HLA associations in insulin-dependent diabetes: search for heterogeneity in different groups of patients from a homogeneous population. Tissue Antigens. 1986 Oct;28(4):237–244. doi: 10.1111/j.1399-0039.1986.tb00489.x. [DOI] [PubMed] [Google Scholar]
  15. Tait B. D., Propert D. N., Harrison L., Mandel T., Martin F. I. Interaction between HLA antigens and immunoglobulin (Gm) allotypes in susceptibility to type I diabetes. Tissue Antigens. 1986 May;27(5):249–255. doi: 10.1111/j.1399-0039.1986.tb01529.x. [DOI] [PubMed] [Google Scholar]
  16. Thomson G. HLA DR antigens and susceptibility to insulin-dependent diabetes mellitus. Am J Hum Genet. 1984 Nov;36(6):1309–1317. [PMC free article] [PubMed] [Google Scholar]
  17. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]

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