Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers

M. F. Frecker, M. Preus, L. Kozma, E. Krasrits, V. Stenszky, C. Balazś, N. R. Farid

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In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than am ong controls (χ2 = 4.71, p<0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patients clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster. Although Gm interacted with HLA in enhancing the susceptibilitty Graves' disease (odds ratio DR3+ fb+ is 8.49, DR3+ fb- is 5.08, and DR3- fb+ is 1.42), this phenotype was distributed equally between the two clusters (48% in C1 and 58% in C2). We conclude that the use of HLA together with relatively few clinical characteristics results in the segregation of a severe and mild for of Graves' disease, and defines which individuals will respond to treatment with antithyroid drugs.

Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalMolecular Biology and Medicine
Issue number1
Publication statusPublished - Nov 12 1986


ASJC Scopus subject areas

  • Genetics(clinical)
  • Molecular Biology

Cite this

Frecker, M. F., Preus, M., Kozma, L., Krasrits, E., Stenszky, V., Balazś, C., & Farid, N. R. (1986). Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers. Molecular Biology and Medicine, 3(1), 63-71.