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Lack of association of interleukin-18 gene polymorphisms with susceptibility of Japanese populations to Graves' disease or Graves' ophthalmopathy.

OBJECTIVE
To investigate whether polymorphisms of interleukin (IL)-18 gene confer susceptibility to Graves' disease (GD) and Graves' ophthalmopathy (GO).


DESIGN
We performed a case control study on polymorphisms of IL-18 gene in Japanese patients with GD (n = 435), and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n = 255). The C-4675G, C-607A, and G-137C polymorphisms in the promoter region and A105C (exon 5) polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes, sequence-specific PCR, and PCR-direct sequencing methods.


RESULTS
None of the polymorphisms in the IL-18 gene were associated with development of Graves' disease. The CC genotype and C allele frequencies of IL-18 gene G-137C polymorphism tended to be greater in patients with ophthalmopathy than in patients without evident ophthalmopathy. However, the differences were not statistically significant. Although there were three major haplotypes, none of the haplotypes were statistically associated with susceptibility to GD or ophthalmopathy.


CONCLUSIONS
These results suggest that IL-18 gene polymorphisms are not major genetic factors for susceptibility to GD in a Japanese population. Further studies with adequate sized data set in the subset analyses for GO are needed.