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  • Title: Graves' ophthalmopathy and gene polymorphisms in interleukin-1alpha, interleukin-1beta, interleukin-1 receptor and interleukin-1 receptor antagonist.
    Author: Khalilzadeh O, Anvari M, Esteghamati A, Mahmoudi M, Tahvildari M, Rashidi A, Khosravi F, Amirzargar A.
    Journal: Clin Exp Ophthalmol; 2009 Aug; 37(6):614-9. PubMed ID: 19702713.
    Abstract:
    PURPOSE: Interleukin-1 (IL-1) is known to have an important role in pathogenesis of Graves' ophthalmopathy (GO). Polymorphisms in IL-1 gene have been associated with autoimmune reactions. This study aimed to investigate the association of GO with single-nucleotide polymorphisms (SNPs) in the IL-1 family (IL-1alpha, IL-1beta, IL-1 receptor [IL-1R] and IL-1 receptor antagonist [IL-1RA]). METHODS: A total of 57 patients of Graves' disease without GO, 50 patients with GO and 140 healthy controls were enrolled. Patients were recruited consecutively from the outpatient endocrine clinic of a large university general hospital. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the following polymorphisms were determined: IL-1alpha (-889C/T), IL-1beta (-511C/T), IL-1beta (+3962C/T), IL-1R (Pst-1 1970C/T) and IL-1RA (Mspa-1 11100C/T). Genotype distributions among patients were in Hardy-Weinberg equilibrium for all polymorphisms. RESULTS: Among the five SNPs studied, the frequencies of the T allele and the TT genotype of IL-1alpha (-889C/T) were significantly higher among patients with GO than those without GO (odds ratio [OR] = 2.16, 95% confidence interval [CI] = 1.25-3.74; P = 0.006 and 5.67, 95% CI = 1.66-49.34; P = 0.005, respectively). For IL-1RA (Mspa-1 11100C/T), the frequencies of the C allele and the CC genotype were significantly higher among patients with GO (OR = 2.31, 95% CI = 1.34-4.00; P = 0.004 and 6.73 95% CI = 1.94-23.36; P = 0.004, respectively; P < 0.01). No significant association was found for other SNPs. CONCLUSION: This is the first study to show a positive correlation between polymorphisms in the IL-1alpha and IL-1RA genes and susceptibility to GO. These findings promote further research into genetic correlates of GO.
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