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ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease.
- Source :
- Pharmacogenomics Journal; Feb2013, Vol. 13 Issue 1, p52-59, 8p
- Publication Year :
- 2013
-
Abstract
- 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<superscript>−1</superscript> (n=70) or 1 g kg<superscript>−1</superscript> 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<superscript>−1</superscript>), 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1470269X
- Volume :
- 13
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Pharmacogenomics Journal
- Publication Type :
- Academic Journal
- Accession number :
- 85039090
- Full Text :
- https://doi.org/10.1038/tpj.2011.45