LACK OF ASSOCIATION OF GRAVES-DISEASE WITH THE A2 ALLELE OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE IN A WHITE EUROPEAN POPULATION

Objective: To assess whether the A2-type IL-1RA polymorphism is associ ated with Graves' disease and Graves' ophthalmopathy. Several reports have described a genetic association between the A2 allele of the inte rleukin-1 receptor antagonist (IL-1RA) gene and certain inflammatory a nd autoimmune diseases, suggesting that certain loci within the IL-1-r elated genes may modulate the autoimmune inflammatory response. Recent ly we demonstrated marked differences in the expression and regulation of IL-1RA gene and protein between orbital fibroblasts derived from p atients with active Graves' ophthalmopathy and healthy individuals. De sign: A total of 144 white European patients with Graves' disease were genotyped to compare their IL-1RA A2 allele frequency with that of 17 4 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 Gra ves' disease and the control group. Moreover. presence or absence of G raves' ophthalmopathy in patients with Graces' 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 associatio n between the IL-1RA A2 allele and Graves' disease or Graves' ophthalm opathy in our study population, Thus the A2-type IL-1RA gene polymorph ism does not appear to indicate an increased susceptibility to develop Graves' disease and Graves' ophthalmopathy. Mechanisms unrelated to t he IL-1RA A2 allele may be responsible for altered IL-1RA production w ithin the orbital tissues in Graves' ophthalmopathy.