Eur J Endocrinol
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DOI: 10.1530/eje.0.1380686
European Journal of Endocrinology, Vol 138, Issue 6, 686-690
Copyright © 1998 by European Society of Endocrinology
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Articles

Lack of association of Graves' disease with the A2 allele of the interleukin-1 receptor antagonist gene in a white European population

T Muhlberg, M Kirchberger, C Spitzweg, F Herrmann, HJ Heberling, and AE Heufelder

Department of Internal Medicine, Klinikum Innenstadt, Ludwig-Maximilians-Universitat, Munchen, Germany.

OBJECTIVE: To assess whether the A2-type IL-1RA polymorphism is associated with Graves' disease and Graves' ophthalmopathy. Several reports have described a genetic association between the A2 allele of the interleukin-1 receptor antagonist (IL-1RA) gene and certain inflammatory and autoimmune diseases, suggesting that certain loci within the IL-1-related genes may modulate the autoimmune inflammatory response. Recently, we demonstrated marked differences in the expression and regulation of IL-1RA gene and protein between orbital fibroblasts derived from patients with active Graves' ophthalmopathy and healthy individuals. DESIGN: A total of 144 white European patients with Graves' disease were genotyped to compare their IL-1RA A2 allele frequency with that of 174 healthy controls. METHODS: The polymerase chain reaction was used to amplify the pentallelic variable-number tandem-repeat locus in intron 2 of the IL-1RA gene. RESULTS: We found no significant differences in IL-1RA A2 allele frequencies (0.20 and 0.26 respectively) and IL-1RA A2 carriage rates (31% and 40% respectively) between patients with Graves' disease and the control group. Moreover, presence or absence of Graves' ophthalmopathy in patients with Graves' disease was not related to significant differences in IL-1RA A2 allele frequencies and IL-1RA A2 carriage rates. CONCLUSIONS: Our data do not support an association between the IL-1RA A2 allele and Graves' disease or Graves' ophthalmopathy in our study population. Thus the A2-type IL-1RA gene polymorphism does not appear to indicate an increased susceptibility to develop Graves' disease and Graves' ophthalmopathy. Mechanisms unrelated to the IL-1RA A2 allele may be responsible for altered IL-1RA production within the orbital tissues in Graves' ophthalmopathy.


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