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

M. Anvari, O. Khalilzadeh, A. Esteghamati, S. A. Esfahani, A. Rashidi, A. Etemadi, M. Mahmoudi, A. A. Amirzargar

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


PurposeIn 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-α, IFN-γ, IL-2, and IL-6, with GO in a sample of Iranian adults.MethodsA 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-α(308A/G, 238A/G), INF-γ(UTR 5644A/T), IL-2 (-330T/G, 166G/T), and IL-6 (174C/G, nt565A/G). A corrected (for multiple testing) P-value (Pc) less than 0•05 was considered statistically significant.ResultsThe IL-12 1188C allele (odds ratio (OR)=2•65, Pc 0•01) and CC genotype (OR=7•58, Pc 0•01) were significantly more common in patients with GO than in patients without GO. The TNF-α238A allele was more frequent in patients with GO than in patients without GO (OR=2•99, Pc 0•05). The frequency of the IFN-γUTR 5644T allele (OR=2•67, Pc 0•05), AT genotype (OR=13•33, P c 0•05), and TT genotype (OR=18•46, Pc 0•01) was significantly higher among patients with GO than patients without GO. No significant association was found for other polymorphisms.ConclusionsWe demonstrated that specific polymorphisms in IL-12, IFN- γ, and TNF-αgenes are associated with susceptibility to GO in the Iranian population. Our results open a new perspective to genetic correlates of GO.

Original languageEnglish (US)
Pages (from-to)1058-1063
Number of pages6
Issue number6
StatePublished - Jun 2010
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant from Tehran University of Medical Sciences (TUMS), Tehran, Iran.


  • Gene
  • Grave?s disease
  • Interleukin
  • Ophthalmopathy
  • Polymorphism


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