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 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.


METHODS
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.
Department of Internal Medicine, Klinikum Innenstadt, Ludwig-Maximilians-Universität, München, Germany.
T
T
Mühlberg
M
M
Kirchberger
C
C
Spitzweg
F
F
Herrmann
H J
HJ
Heberling
A E
AE
Heufelder
D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005858:Germany; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins