Background: Approximately 8-38% of children with Kawasaki disease (KD) will have persistent or recrudescent fever after initial intravenous immunoglobulin (IVIG) treatment and are at increased risk for development of coronary artery abnormalities. Using genetic markers may be helpful to identify the high-risk group of IVIG-resistant patients for aggressive treatment. The aim of this study was to evaluate the associations between 4 potential polymorphisms in the interleukin (IL)-1 family of genes and initial IVIG treatment failure in KD children. Methods and Results:A total of 156 KD children (136 with and 20 without a response to IVIG treatment) who were treated with high-dose IVIG (2 g/kg) within 10 days of fever onset were recruited. Polymerase chain reaction and Taqman assays were used for genotyping. A significant increase in IVIG resistance risk was observed for IL-1B −511 TT and IL-1B −31 CC genotypes (adjusted odds ratio (AOR) 5.27, 95% confidence interval (CI) 1.69-16.38, P=0.004; AOR 3.95, 95%CI 1.26-12.41, P=0.019, separately). The diplotype TC/TC (at IL-1B −511 and −31) also showed a significantly increased risk of IVIG resistance (AOR 4.32, 95%CI 1.36-13.71, P=0.013). Conclusions:The IL-1B −511 TT and IL-1B −31 CC genotypes or the TC/TC diplotype may be associated with initial IVIG treatment failure in Taiwanese children with KD. (Circ J 2010; 74: 544 - 551)

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Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > C and −592 A > C for KD cases was observed (Ppermutation = 0.029 and Ppermutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p = 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.