Association of CTLA-4 and IL-13 gene polymorphisms with Graves' disease and ophthalmopathy in Chinese children.

PURPOSE: The frequency of childhood Graves' disease (GD) in Hong Kong Chinese is among the highest in the world but childhood Graves' ophthalmopathy (GO) appears to have milder clinical severity than does the adult disease. This study was conducted to investigate CTLA-4 and IL-13 polymorphisms in Chinese pediatric patients with GD and GO.

METHODS: Recruited for the study were 177 childhood patients with GD (age range, 2-16 years) and 151 unrelated control subjects (age range, 4-16 years) for genotype analysis of IL-13 single-nucleotide polymorphisms (SNPs) (-1112C/T and 2044G/A), CTLA-4 SNPs (-318C/T, 49A/G, and CT60A/G), and the repeat length of (AT)n in the 3' untranslated region (UTR) of CTLA-4.

RESULTS: The patients with GD revealed higher frequencies of CTLA-4 49 GG genotype and G alleles than did the control subjects (P = 0.005 and P = 0.03, respectively). The CT60 GG genotype and G alleles were more prevalent in GD (P = 0.07 and P = 0.02, respectively). The CTLA-4 SNPs (-318C/T, 49A/G, and CT60A/G) were in the same haplotype block, and the CGG haplotype was associated with GD (P = 0.0071) but not GO. The shortest allele of (AT)n was protective against GD (P = 8.4 x 10(-6)). The IL-13 SNPs did not affect GD or GO risk. IL-13 -1112C/T was associated with IgE elevation (P = 0.044) and 2044G/A with proptosis (P = 0.02), but these associations became insignificant after Bonferroni correction (P = 0.22 and 0.10, respectively).

CONCLUSIONS: Three SNPs and the AT repeat length in CTLA-4 conferred susceptibility to childhood GD, whereas IL-13 polymorphisms did not. No association was found between CTLA-4 and IL-13 with GO.