Association of CTLA-4, IL-13 Gene polymorphism with Graves' disease and ophthalmopathy in Chinese children
Kelvin K.L. Chong 1,
Sylvia W.Y. Chiang 1,
Gary W.K. Wong 2,
Pancy O.S. Tam 1,
Tsz Kin Ng 1,
Yi Jun Hu 3,
Gary Hin-Fai Yam 1,
Dennis S.C. Lam 1,
and
Chi-Pui Pang 4*
1 Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
2 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
3 Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Joint Shantou International Eye Center, Shantou University Medical College, Shantou, China
4 Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong Kong, Hong Kong, China
* To whom correspondence should be addressed. E-mail: cppang{at}cuhk.edu.hk.
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Abstract |
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Purpose: Childhood Graves' disease (GD) in Chinese is among the most frequent in the world but childhood Graves' ophthalmopathy (GO) is milder in clinical severity than adults. We investigated CTLA-4 and IL-13 polymorphisms in Chinese pediatric patients with GD and GO.
Methods: We recruited 177 childhood GD patients (age range 2-16) and 151 unrelated control subjects (age range 4-16) for genotype analysis of IL-13 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'UTR of CTLA-4.
Results: GD patients have higher frequencies of CTLA-4 49 GG genotype and G alleles than controls (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=8.4E-06). The IL-13 SNPs did not affect GD or GO risk. IL-13 -1112C/T was mildly associated with IgE elevation (p=0.044) and 2044G/A with proptosis (p=0.02), but after bonferroni correction the associations became insignificant (p=0.22 and 0.10 respectively). The AA genotype of IL-13 2044G/A was more frequent in GO patients with proptosis than those without, 24.7% vs 4.5%
Conclusions: Three SNPs and the AT repeat length in CTLA-4 conferred susceptibility to childhood GD, while IL-13 polymorphisms did not. We found no association between CTLA-4 and IL-13 with GO, but IL-13 2044G/A (R130Q) may contribute to proptosis.
Key Words:
CTLA-4, IL-13, Graves' ophthalmopathy, children, Chinese
