期刊
PHARMACOGENOMICS JOURNAL
卷 13, 期 1, 页码 52-59出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2011.45
关键词
Kawasaki's disease; ITPKC; CASP3; SNP; IVIG resistance; coronary artery lesion
资金
- Millennium Project, Japan Kawasaki Disease Research Center
- Ministry of Health, Labour, and Welfare [0401040]
- Grants-in-Aid for Scientific Research [23591529, 22591190] Funding Source: KAKEN
Functional single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) (rs28493229) and caspase-3 (CASP3) (rs113420705; formerly rs72689236) are associated with susceptibility to Kawasaki's disease (KD). To evaluate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) unresponsiveness, we investigated 204 Japanese KD patients who received a single IVIG dose of 2 g kg(-1) (n = 70) or 1 g kg(-1) daily for 2 days (n = 134). The susceptibility allele of both SNPs showed a trend of overrepresentation in IVIG non-responders and, in combined analysis of these SNPs, patients with at least 1 susceptible allele at both loci had a higher risk for IVIG unresponsiveness (P = 0.0014). In 335 prospectively collected KD patients who were treated with IVIG (2 g kg(-1)), this 2-locus model showed a more significant association with resistance to initial and additional IVIG (P = 0.011) compared with individual SNPs. We observed a significant association when all KD patients with coronary artery lesions were analyzed with the 2-locus model (P = 0.0031). Our findings strongly suggest the existence of genetic factors affecting patients' responses to treatment and the risk for cardiac complications, and provide clues toward understanding the pathophysiology of KD inflammation. The Pharmacogenomics Journal (2013) 13, 52-59; doi:10.1038/tpj.2011.45; published online 11 October 2011
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据