Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves' disease.

Among genetic factors that may contribute to the development and progression of Graves' disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (-1098T/G, -590T/C, -33C/T), IL-10 (-1082A/G, -819C/T, -592C/A) and TGF-beta (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 -1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 -33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 -1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 -819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 -592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-beta +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-beta +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 -590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.