Systematic confirmation study of GWAS-identified genetic variants for Kawasaki disease in a Chinese population.

Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with Kawasaki disease (KD). In this study, we replicated the associations of 10 GWAS-identified SNPs with KD in a Han Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression, and cumulative effect of non-risk genotypes were also performed. Although none of the SNPs reached the corrected significance level, 4 SNPs showed nominal associations with KD risk. Compared with their respective wild type counterparts, rs1801274 AG+GG genotypes and rs3818298 TC+CC genotypes were nominally associated with the reduced risk of KD (OR = 0.77, 95% CI = 0.59-0.99, P = 0.045; OR = 0.74, 95% CI = 0.56-0.98, P = 0.038). Meanwhile, rs1801274 GG genotype, rs2736340 CC genotype or rs4813003 TT genotype showed a reduced risk trend (OR = 0.57, 95% CI = 0.35-0.93, P = 0.024; OR = 0.46, 95% CI = 0.26-0.83, P = 0.010; OR = 0.64, 95% CI = 0.43-0.94, P = 0.022), compared with rs1801274 AG+AA genotypes, rs2736340 CT+TT genotypes or rs4813003 TC+CC genotypes, respectively. Furthermore, a cumulative effect was observed with the ORs being gradually decreased with the increasing accumulative number of non-risk genotypes (Ptrend<0.001). In conclusion, our study suggests that 4 GWAS-identified SNPs, rs2736340, rs4813003, rs3818298 and rs1801274, were nominally associated with KD risk in a Han Chinese population individually and jointly.

The roles of Ca2+/NFAT signaling genes in Kawasaki disease: single- and multiple-risk genetic variants.

Ca(2+)/nuclear factor of activated T-cells (Ca(2+)/NFAT) signaling pathway may play a crucial role in Kawasaki disease (KD). We investigated 16 genetic variants, selected by bioinformatics analyses or previous studies, in 7 key genes involved in this pathway in a Chinese population. We observed a significantly or marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR = 1.39, 95% CI = 1.07-1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28, 95% CI = 0.98-1.67, P = 0.066), compared with their wild type counterparts. In classification and regression tree analysis, individuals carrying the combined genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46-3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG genotype. Moreover, a significant dose effect was observed among these three variants (Ptrend < 0.001). In conclusion, this study implicates that single- and multiple-risk genetic variants in this pathway might contribute to KD susceptibility. Further studies on more comprehensive single nucleotide polymorphisms, different ethnicities and larger sample sizes are warranted, and the exact biological mechanisms need to be further clarified.

8p22-23-rs2254546 as a susceptibility locus for Kawasaki disease: a case-control study and a meta-analysis.

8p22-23-rs2254546 was firstly discovered to be associated with Kawasaki disease (KD) susceptibility by a genome-wide association study. However, only one Chinese replication study has been performed so far. To verify this association in another Chinese population, a hospital-based case-control study in Zhejiang province was conducted followed by an integrated meta-analysis, comprising five case-control studies of 1958 cases, 5615 controls and four transmission disequilibrium tests of 503 trios. In our case-control study, significant associations were observed between GG genotype or GG/GA genotypes of rs2254546 and increased KD risk (OR = 1.86, 95% CI = 1.01-3.41, P = 0.045; OR = 1.83, 95% CI = 1.01-3.33, P = 0.048), compared with AA genotype; however, no significant association was found in allelic model (OR = 1.20, 95% CI = 0.96-1.50, P = 0.117). The meta-analysis further revealed that the G allele was significantly associated with the increased KD risk without evidence of heterogeneity (OR = 1.55, 95% CI = 1.42-1.70, P < 0.001). In conclusion, rs2254546 polymorphism might significantly contribute to the risk of KD.

[Six Kawasaki disease patients with acute coronary artery thrombosis].

OBJECTIVE: To improve the awareness of acute coronary artery thrombosis in Kawasaki disease (KD). METHOD: Six KD patients with acute coronary artery thrombosis (Jan. 2004 to Jan. 2013) were studied retrospectively. The basic information, clinical manifestations, laboratory data, echocardiography and electrocardiography (ECG), method and consequence of thrombolytic therapy were analyzed. RESULT: The mean age of patients with coronary artery thrombosis (5 males and 1 female) was (17.2 ± 11.3) months.Five cases had thrombosis in left coronary artery (LCA), and four cases had thrombosis in aneurysm of left anterior descending artery (LAD). One case had thrombosis in both left and right coronary artery (RCA).One case died. Maximum thrombus was about 1.60 cm × 0.80 cm, locating in LAD. The diameter of LCA and RCA was (0.44 ± 0.07) cm and (0.45 ± 0.07) cm. Two patients showed abnormal ECG. Case 3 showed ST segment depression in lead V5. Case 6 showed myocardial infarction.In acute phase of KD, three patients received treatment with intravenous immunoglobin (IVIG), five patients were treated with aspirin.In sub-acute and convalescent phase of KD, all patients were treated with low-dose aspirin.Warfarin and dipyridamole were applied in 5 patients. All cases were treated with thrombolytic therapy using urokinase and/or heparin. After thrombolytic therapy, echocardiography showed thrombolysis in four cases and no change in one.One patient died of myocardial infarction. CONCLUSION: Most of acute coronary thrombosis in KD occurred in LAD. KD patients with coronary artery thrombosis are at risk of sudden death due to myocardial infarction.

Cardiogenic shock: do not forget the possibility of Kawasaki disease.

We report the case of a six-year-old boy who presented with cardiogenic shock due to Kawasaki disease (KD). He was misdiagnosed at first as septic shock. After careful examination, he was diagnosed as KD complicated with acute coronary syndrome, which leads to cardiogenic shock. Cardiogenic shock is often neglected as a complication of KD, and it tends to be misdiagnosed. We hereby call attention to KD, in some cases of which, it can lead to acute coronary syndrome in the acute phase.