Association of Graves＇ disease and Graves＇ ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene

Objective： To investigate the association of Graves＇ disease and Graves＇ ophthalmopathy with the C/T transition polymorphism at position -318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 （CTLA-4） gene. Methods： Thirty-three patients with ophthalmopathy of Graves＇ disease, fifty-six Graves＇ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism （PCR-RFLP）. Comparisons were made of gene frequencies and allele frequencies between the groups. Results： The gene frequencies of CT and allele frequencies of T were much higher in Graves＇ patients with ophthalmopathy than that in the group without ophthalmopathy （P=-0.020, P=-0.019）. The gene frequencies of GG and allele frequencies of G in patients with Graves＇ disease were significantly increased as compared with control group （P=0.008, P=0.007）. The data suggest that smokers with Graves＇ disease seemed to be more predisposed to ophthalmopathy than non-smokers （P=0.018）. Conclusion： Our results suggest that an allele of T at position -318 of promoter is associated with genetic susceptibility to Graves＇ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves＇ disease instead. Smoking is believed to be a major risk factor for ophthalmopathy.