Objective: To investigate the relevance of tumor necrosis factor-alpha (TNF-alpha) gene -863C/A polymorphism with thyroid-associated ophthalmopathy (TAO).
Methods: TNF-alpha gene polymorphism at position -863 was determined by PCR-RFLP in 76 normal people, 54 patients with TAO and 60 patients with autoimmune thyroid disease (AITD) who had no ophthalmopathy. All the subjects were collected from July 2002 to December 2003 in out-patient department of endocrinology in the hospital. The difference of genotype and the variation of allele frequencies were analyzed by Chi-square test.
Results: (1) Frequencies distribution of CA + AA genotype in TAO, non-ophthalmopathy and control groups were 46.3%, 30.0%, 25.0% respectively, and allele A were 27.8%, 15.0%, 12.5% for those three groups respectively. (2) Frequencies of allele A in TAO group were significantly higher than those in non-ophthalmopathy and control groups (P = 0.018 and 0.002 respectively). (3) When the three groups were stratified according to sex, frequencies of -863 CA + AA genotype and allele A in male TAO patients were significantly higher than those in control group (OR = 4.31, P = 0.019; OR = 4.81, P = 0.003) and non-ophthalmopathy group (OR = 4.87, P = 0.027; OR = 5.38, P = 0.008). No significant difference was found in female patients (P > 0.05). (4) Frequencies of CA + AA genotype and allele A in TAO patients with 5 + 6 grade were significantly higher than those in non-ophthalmopathy group (CA + AA genotype: OR = 20.68, P = 0.021; allele A: OR = 39.67, P < 0.001).
Conclusion: Allele A of TNF-alpha gene at position -863 may be associated with TAO especially in male patients.