Genetic susceptibility to Graves' ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

Eye

Volume 6 - Number

Article Type: ---- Unspecified ----
Abstract:

Purpose In order to investigate the underlying genetic mechanisms of Graves' ophthalmopathy (GO), we examined the association between single-nucleotide polymorphisms in five important proinflammatory cytokines, namely IL-12, TNF-alpha, IFN-gamma, IL-2, and IL-6, with GO in a sample of Iranian adults. Methods A total of 57 patients with 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. Genotype and allele frequencies of the following proinflammatory cytokines were compared between the groups: IL-12 (-1188A/C), TNF-alpha (-308A/G, -238A/G), INF-gamma (UTR 5644A/T), IL-2 (-330T/G, 166G/T), and IL-6 (-174C/G, nt565A/G). A corrected (for multiple testing) P-value (P(c)) less than 0.05 was considered statistically significant. Results The IL-12 -1188C allele (odds ratio (OR) 2.65, P(c) < 0.01) and CC genotype (OR 7.58, P(c) < 0.01) were significantly more common in patients with GO than in patients without GO. The TNF-alpha -238A allele was more frequent in patients with GO than in patients without GO (OR = 2.99, Pc < 0.05). The frequency of the IFN-gamma UTR 5644T allele (OR = 2.67, P(c) < 0.05), AT genotype (OR = 13.33, P(c) < 0.05), and TT genotype (OR = 18.46, P(c) < 0.01) was significantly higher among patients with GO than patients without GO. No significant association was found for other polymorphisms. Conclusions We demonstrated that specific polymorphisms in IL-12, IFN-gamma, and TNF-alpha genes are associated with susceptibility to GO in the Iranian population. Our results open a new perspective to genetic correlates of GO. Eye (2010) 24, 1058-1063; doi: 10.1038/eye.2009.244; published online 2 October 2009