ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease.

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.

[Long-term follow-up results on Bentall's and our modified procedure].

Replacement of the ascending aorta and the aortic valve with composite graft, including reimplantation of coronary ostia, were performed in 84 patients from October, 1978 to December, 1989. Annuloaortic ectasia was the most common indication for surgery (76 patients). Thirty patients (36%) had the Marfan syndrome. Thirty-five patients were performed with original Bentall's procedure. Thirty patients were carried out with our modified technique like Inberg's, the coronary arteries were excised with attachment of the selected piece of the aortic wall, and implanted to the tube prosthesis with continuous suture. Nineteen patients were operated with modified technique by Cabrol or other interposition graft method. The actuarial free of death related to the operation of 4 years was 83%, 88%, and 74% (p = NS) in each methods respectively. The complications of anastomosis, for example, leakage and dilatation of coronary ostia were not seen in our modified Bentall's procedure. In conclusion, our modified method is proved to be reliable and competent.