Although an association between the human leukocyte antigen (HLA) allele DR3 and Graves' disease (GD) is well documented, the potential role of non- HLA-linked alleles in susceptibility to GD is an area of active investigation. In an attempt to study the potential role of two non-HLA susceptibility alleles in GD and Graves' ophthalmopathy, we examined 286 North American Caucasian individuals (145 normal controls and 141 individuals with GD) for the presence of the A2 allele of the interleukin-1 (IL-1) receptor antagonist gene. In addition, we examined a subset of this population (83 normal controls and 89 individuals with GD) for a specific polymorphism within exon 5 of the IL-1α gene. We found the A2 allelic frequencies (0.25 and 0.23, respectively) and carriage rates (43% and 41%, respectively) in the two groups to be nearly identical. However, findings in the subgroup of patients with the extrathyroidal manifestations of GD (Graves' ophthalmopathy, pretibial dermopathy, and acropachy) suggested a trend toward a higher prevalence of the A2 allele in patients with more severe disease. The allelic frequency (0.28) and carriage rate (47%) of the IL-1α exon 5 polymorphism in individuals with GD were nearly identical to those of the control population (0.28% and 45%, respectively). In summary, we were unable to demonstrate an association between these alleles and GD in our study population. We conclude that neither the A2 allele of the IL-1 receptor antagonist gene nor the IL-1α exon 5 polymorphism confers increased susceptibility to GD.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical