Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease

被引:65
作者
Burns, JC
Shimizu, C
Shike, H
Newburger, JW
Sundel, RP
Baker, AL
Matsubara, T
Ishikawa, Y
Brophy, VA
Cheng, S
Grow, MA
Steiner, LL
Kono, N
Cantor, R
机构
[1] Univ Calif San Diego, Sch Med, Dept Pediat 0830, La Jolla, CA 92093 USA
[2] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA
[3] Boston Childrens Hosp, Dept Pediat, Boston, MA USA
[4] Yamaguchi Univ, Dept Pediat, Yamaguchi, Japan
[5] Roche Mol Syst, Dept Human Genet, Alameda, CA USA
[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Pediat, Los Angeles, CA USA
关键词
pediatrics; vasculitis; coronary artery aneurysm; Th2 immune response; transmission disequilibrium test; polymorphism;
D O I
10.1038/sj.gene.6364225
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease ( KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 ( IL-4) C( -589) T allele ( P 0.03). Asymmetric transmission of the IL-4 C( -589) T was replicated in a second, independent cohort of 60 trios ( P 0.05, combined P 0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 ( CSF2), IL-13, and transcription factor 7 ( TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor ( FC epsilon R2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility.
引用
收藏
页码:438 / 444
页数:7
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