The Association Of TNF-α Gene Polymorphisms With Thyroid Associated Ophthalmopathy

Objective:To investigate the association of TNF-a gene-863C/A、-1031T/C、-238G/A polymorphisms with thyroid associated ophthalmopathy(TAO)and disease severity in Han population of North China.Methods:A total of 158 patients with Graves’ disease without GO,154 patients with TAO,and 152 healthy controls were enrolled.According to EUGOGO classification,the TAO group was divided into 3 subgroups:the mild group with 52 patients,the moderate-to-severe group with 55 patients and the sight-threatening group with 47 patients.Genomic DNA was extracted from peripheral blood using magnetic beads and genotyping was detected with the TaqMan-MGB real time PCR method.Statistical analysis was performed using the Chi-squared test and P-values were corrected by the Bonferroni method.Results:Polymorphisms of TNF-a gene-863C/A、-1031T/C、-238G/A existed in the 464 subjects.The TNF-a-863 AC+AA genotype was significantly more common in patients from moderate-to-severe+ sight-threatening TAO group(Pc<0.05)than in healthy controls and patients from mild TAO group(P<0.05).The TNF-a-863A allele was more frequent in patients with moderate-to-severe+ sight-threatening GO than in healthy controls(P<0.05).The frequency of TNF-a-863A allele in male GD without GO+ mild TAO group was significantly higher than in control group.The TNF-α-1031T/C CT+CC genotype was significantly more common in moderate-to-severe+sight-threatening TAO group than in healthy control group and GD without GO+ mild TAO group(Pc<0.05).No significant difference of-1031C allele frequency was found among groups.The TNF-α-1031T/C CT+CC genotype was significantly more frequent in sight-threatening TAO group and moderate-to-severe+ sight-threatening TAO group than in mild TAO group(Pc<0.05,P<0.05,respectively).The frequency of CT+CC genotype in male moderate-to-severe+ sight-threatening group was significantly higher than in the male control group(Pc<0.05).No significant association was found between TNF-a-238G/A polymorphisms and TAO.Conclusions:There were TNF-α gene-863C/A、-1031T/C、-238G/A polymorphisms in Han population of North China.The polymorphisms of TNF-a-863C/A、-1031T/C were associated with TAO and disease severity.TNF-a-863C/A、TNF-α-1031T/C may be the susceptibility genes of TAO in North China Han population.No relationship was found between TNF-a-238G/A polymorphisms and TAO susceptibility.