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Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7 days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the
PELI1
gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the
PELI1
gene. Multivariate analysis also showed that a serum albumin level of 3.6 g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34–5.68;
P
= 0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the
PELI1
gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.