Association Study Of Suppressor Of Cytokine Signaling3and Graves’ Ophthalmopathy

Background and objective:Thyroid associated ophthalmopathy is the disease of orbital tissue inflammation, and closely associated with Graves’ disease. The morbidityof the disease is the firstin adult orbital disease. A large number of inflammatory factors involved in the disease process, but the exact pathogenesis is not clear. Suppressor of cytokine signaling-3as a negative regulator of inflammatory factoroccurs in a variety of inflammatory diseases, and plays an important role. This study was to investigate the relationship between SOCS3protein and thyroid associated ophthalmopathy.Methods:1. Take the orbital adipose tissue of patients with thyroid associated ophthalmopathy and the normal.The expression of SOCS3protein was detected in the orbital adipose tissue of patients. Immunofluorescence methodwas used.2. Cultured fibroblasts were from the orbital adipose tissue of the patients with thyroid associated ophthalmopathy and the normal. The differential expression of SOCS3mRNA and protein was detected in two groups. Real-time PCR and Western blot were used.3.270cases of patients with Graves’ disease were collected, and were divided into Graves’ disease with eye disease group (114cases) and Graves’ disease without ophthalmopathy group (156cases). Peripheral blood mononuclear cells (PBMC)taken from Graves’ disease patients with and without eye disease, was used for the establishment of lymphoblastoid cell lines transformed with EB virus (EBV-LCLs).The differential expression of SOCS3mRNA and protein was detected in two groups. Real-time PCR and Western blot were used.SOCS3gene5loci (rs12952093, rs4969170, rs4969168, rs4969169, and rs2280148) were genotyped by the ligase detection reaction-PCR(LDR-PCR) gene sequencing typing technique for all patients. The relationship between the SOCS3gene and the gene type of thyroid associated ophthalmopathy patients was analyzed by multivariate Logistic regression analysis. To observe the effectof the genotype associated with thyroid associated ophthalmopathy on the expression of SOCS3. Real-time PCR and Western blot were used. Results:1.The expression level of SOCS3in orbital adipose tissue from patients with thyroid associated ophthalmopathy was significantly higher than in normal people (P<0.05).2. The expression of SOCS3mRNA and protein in the fiber cell frompatientswith thyroid associated ophthalmopathy was significantly higher than in normal people (P <0.05).3. The expression level of SOCS3mRNA and EBV-LCLs protein in Graves’ disease patients with ophthalmopathy was increased significantly (P<0.05).4. The factors of age and sex, BMI, smoking, goiter, thyroid nodules, myxedema, Graves disease treatment (drugs, radiation therapy, and these factors of hypertension after thyroidectomy) were adjusted for multivariate Logistic regression analysis.It is showed that the increased risk of thyroid associated ophthalmopathy was associated with SOCS3rs4969170AA genotype (OR=3.5,95%CI1.6to7.5, P=0.001). The association of SOCS3rs12952093, rs4969168, rs4969169and rs2280148and thyroid associated ophthalmopathy was not statistically significant. The expression of SOCS3mRNA and protein in EBV-LCLs of patients with thyroid associated ophthalmopathy with SOCS3rs4969170AA genotype increased significantly (P<0.05). Conclusion:SOCS3rs4969170AA genotype is associated with increased risk of thyroid associated ophthalmopathy. In patients with thyroid associated ophthalmopathy, SOCS3rs4969170may be a functional SNP, affecting the expression of SOCS3.