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

Abstract

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.

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

“…The -238A/G polymorphism did not have a significant association with GD in our series. One reason for this inconsistency with previous reports may be related to ethnic differences, as we have previously demonstrated for other cytokine gene polymorphisms [19]. Sample size difference between studies is another potential explanation.…”

An association of interleukin-10 gene polymorphisms with Graves’ disease in two Chinese populations

“…There were three reported studies of a genetic association of the two shared SNPs (rs1800896 and rs1800872) with GD susceptibility from Iran, Taiwan, and the UK [9,13,14]. All three studies were independent, and the data were in Hardy-Weinberg equilibrium.…”

“…The gene encoding IL-10 is located at Chr.1q32.2. A number of previous studies have identified a significant association between autoimmune diseases and three of the most characterized singlenucleotide polymorphisms (SNPs) in the promoter region of IL-10, positions -1082 A/G (rs1800896), -819 T/C (rs1800871), and absolute-link -592 A/C (rs1800872) [9].…”

“…The rs1800896 (A-1082G) and rs1800872 (A-592C) polymorphisms have been revealed to may be genetic risk factors for GD [9].To investigate the relationship between the IL-10 gene and susceptibility to GD, we performed two independent case-control association studies with Chinese GD patients targeting SNP genotyping and haplotype analysis. We also performed a meta-analysis combining current and previously reported data to evaluate the effect of the two polymorphisms on the patient susceptibility to GD.…”

Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

“…It may be worth noting here that, clinically, the role of IL10 for the pathogenesis of Graves' disease can also be suspected by studies on IL10 gene polymorphisms (Khalilzadeh et al 2010) and on serum IL10 concentrations in patients with autoimmune thyroid diseases (Takeoka et al 2004). …”