Clinical Study
Eye advance online publication 2 October 2009; doi: 10.1038/eye.2009.244
Genetic susceptibility to Graves' ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes
M Anvari1, O Khalilzadeh1, A Esteghamati2, S A Esfahani1, A Rashidi2, A Etemadi3, M Mahmoudi1,4 and A A Amirzargar1,4
- 1Molecular Immunology and Immunogenetics Research Center, Tehran University of Medical Sciences, Tehran, Iran
- 2Endocrinology and Metabolism Research Center, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
- 3Department of Epidemiology and Biostatistics, School of Public Heath, Tehran University of Medical Sciences, Tehran, Iran
- 4Immunogenetics Lab, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Correspondence: AA Amirzargar, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Keshavarz Blvd., Poursina St, Tehran 13145-784, Iran. Tel: +9821 644 32465; Fax: +9821 664 22337; E-mail: amirzargar.ali@gmail.com
Received 2 February 2009; Revised 25 August 2009; Accepted 25 August 2009; Published online 2 October 2009.
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-
, IFN-
, 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-(-308A/G, -238A/G), INF-(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--238A allele was more frequent in patients with GO than in patients without GO (OR=2.99, P
c<0.05). The frequency of the IFN-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- , and TNF-genes are associated with susceptibility to GO in the Iranian population. Our results open a new perspective to genetic correlates of GO.
Keywords:
Grave's disease, ophthalmopathy, interleukin, gene, polymorphism
