Association of Interleukin-1β (IL1B) Polymorphisms with Graves' Ophthalmopathy in Taiwan Chinese Patients

PURPOSE. To evaluate whether variations in the IL1B gene could be associated with Graves' ophthalmopathy (GO) in patients with Graves' disease (GD). METHOD. This case-control study included 471 Taiwan Chinese patients with GD (200 with GO and 271 without GO) and 160 healthy volunteers. Eight single-nucleotide polymorphisms (SNPs) in IL1B were genotyped with an allele-specific extension and ligation assay. RESULTS. In the IL1B SNPs examined, the C allele of rs1143634 was associated with GD, whereas the T/T genotype of the SNPs rs1143634 and rs16944 were less associated with the disease. The A/A genotype of the SNPs rs3917368 and rs1143643, which had the strongest interaction, may increase the risk of GO (P = 0.024 and P = 0.017, respectively). Several GD susceptibility and insusceptibility IL1B haplotypes have been identified, and the Ht4-GCGCCTCC haplotype, composed of eight SNPs and associated with low circulating IL1 beta levels, may be protective against the development of GO (P = 0.025). Moreover, that the GO-susceptible genotype was associated with lower plasma IL1 beta concentrations implies that the origin of GO may go beyond the IL1B polymorphism-associated elevation of circulating IL1 beta. CONCLUSIONS. The data for IL1B polymorphisms and the association of GD and GO with plasma IL1 beta levels show that IL1B polymorphisms may be associated with the development of GD and GO. (Invest Ophthalmol Vis Sci. 2010;51:6238-6246) DOI:10.1167/iovs.09-4965