Association of an IL-4 gene haplotype with Graves disease in children: experimental study and meta-analysis

Investigations of an association between Graves disease (GD) and the IL-4 gene have yielded conflicting results. We performed a case–control study of IL-4 gene polymorphisms possibly associated with GD, as well as a meta-analysis of other such studies. We genotyped IL-4 single nucleotide polymorphisms (SNPs) rs2243250 and rs2243289 in 220 unrelated children with GD and 904 healthy controls. No significant differences between patients and controls were observed in the genotype, allele, or carrier frequencies of the 2 SNPs. The levels of autoantibodies did not differ significantly between the genotypes of each SNP. Linkage disequilibrium between the 2 SNPs was strong in the controls (D′, 0.916; r2, 0.824). Haplotype TA conferred a significant risk of GD (odds ratio = 2.47, 95% confidence interval 1.24–4.95, corrected p value = 0.033). The T allele frequency of rs2243250 was 80.0% in Asians, significantly higher than the 12.6% in Caucasians (p = 1.4 × 10−269). Meta-analysis of data from 8 published reports and our own study did not reveal any significant association between these SNPs and GD. Our study showed an association between the IL-4 gene and GD in children, but only using a haplotype-based method, suggesting that this might be a better approach than evaluating individual SNPs.