Kawasaki disease has become the leading cause of acquired heart disease in children in North America and Japan. The incidence rate of Kawasaki disease varies significantly across regions and races. The first-degree relatives of patients with Kawasaki disease have a significantly higher risk of this disease than the general population. This article reviews the onset of familial Kawasaki disease and possible pathogenesis.
Animals ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications ; genetics ; immunology ; pathology

Child, Preschool ; Family ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics

OBJECTIVES: To provide clues for further study of the relationship between miRNAs and Kawasaki disease (KD) development, and to provide molecular markers for ultimately improve the rate of early diagnosis for KD. METHODS: We collected acute, recovery KD children's plasma and normal samples, then used the miRNAs Assay Chip to screen the differentially expressed miRNAs in the plasma from KD children. Subsequently, miR-455-5p, which had identified via miRNAs assay chip, was validated by quantitative real-time PCR via independent cohort. RESULTS: According to the results of miRNAs Assay chip, we identified a miRNAs panel including 5 miRNAs significantly up-regulated and 5 miRNAs remarkably down-regulated in the plasma from KD children compared to the normal control; miR-455-5p in both of acute and recovery KD children's plasma was remarkably lower than that in the normal control (<0.001, =0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children (=0.007) by independent cohort validation. CONCLUSIONS There are significantly differentially expressed circulating miRNAs between the KD children and normal control. We identified 10 miRNAs dysregulation in the KD children's plasma compared with the normal group. Circulating miR-455-5p in both of acute and recovery KD children's plasma is remarkably lower than that in the normal control, and miR-455-5p may considered as a marker to show the recovery process of KD children. Plasma specific circulating miRNAs play an important role in the early diagnosis of KD and become the new molecular marker of KD in the future.
Biomarkers ; Child ; Humans ; MicroRNAs ; genetics ; Mucocutaneous Lymph Node Syndrome ; genetics ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction

Tumor necrosis factor (TNF) -alpha plays a major role in the pathogenesis of Kawasaki disease (KD), a systemic vasculitis primarily affecting young children. We performed this study to examine the serum levels of TNF-alpha and to investigate a possible relation to promoter polymorphism at positions -238 and -308 in KD patients in Korea. We obtained 48 paired serum samples from 24 patients in the acute and subacute stages of KD, and control sera from 12 age-matched children who were having routine blood samples taken before elective surgical procedures. Our studies showed a significant increase in serum levels of TNF-alpha measured in the acute stage of KD (24.1+/-9.4 pg/mL) compared to those in the subacute stage (11.8+/-5.8 pg/mL; p < 0.01) and normal controls (10.4+/-4.9 pg/mL; p < 0.01). Previous studies report that the presence of the A allele at positions -308 and -238 may be associated with higher TNF-alpha levels. However, our results showed that the frequency of the A allele at position -308 in the KD patients was the same as the controls (2 out of 24, 8.3% vs. 8.3%, odds ratio (OR) = 1.00), while the frequency of the A allele at position -238 in the KD patients was lower than the controls (0/24, 0% vs. 8.3%, OR=0.00) ; this difference though was not statistically significant. We concluded that although TNF-alpha levels were significantly elevated in the acute stage of KD, there was no significant difference in the frequency of the A allele at positions -238 and -308 between the KD and control groups in Korean patients.
Case-Control Studies ; Child, Preschool ; Human ; Korea ; Mucocutaneous Lymph Node Syndrome/*blood/*genetics ; *Polymorphism (Genetics) ; Promoter Regions (Genetics) /*genetics ; Tumor Necrosis Factor/*genetics/*metabolism

OBJECTIVETo study the association between two single nucleotide polymorphisms (rs4810485 and rs1535045 in CD40 gene) and Kawasaki disease (KD) in Han Chinese children.

METHODSA case-control study was performed on 184 children with KD and 206 normal controls. The polymorphisms of two SNPs in CD40 gene were detected using PCR-RFLP.

RESULTSThere were no significant differences in the genotype distribution and allele frequency of SNP rs4810485 in CD40 gene between the KD and normal groups (P>0.05). The genotype distribution of SNP rs1535045 in CD40 gene in the KD group was significantly different from the control group (P<0.05). T allele of SNP rs1535045 was shown as a risk factor for development of KD (OR=1.592, 95%CI: 1.182-2.144, P=0.004). There were no association between the polymorphisms of the two SNPs and coronary artery lesions (P>0.05).

CONCLUSIONSSNP rs1535045 may be associated with the development of KD in Han Chinese children, while SNP rs4810485 may not.

CD40 Antigens ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Coronary Artery Disease ; genetics ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo study the distribution of polymorphism of c.212-37insC (rs3832879) in intron 1 of fibroblast growth factor 23 (FGF23) gene and its association with Kawasaki disease (KD) and coronary artery lesions (CAL).

METHODSForty children with KD were enrolled in this study, among whom 16 children had concurrent CAL. Twenty-six age-matched healthy children were enrolled as controls. PCR and gene sequencing were applied to explore the distribution of polymorphism of c.212-37insC (rs3832879) in FGF23 gene in KD patients and controls.

RESULTSAmong 40 children with KD, 14 (35%) carried the polymorphism of c.212-37insC (rs3832879) in FGF23 gene; among 26 controls, 6 (23%) carried such polymorphism. There was no significant difference in genotype distribution at this locus between the two groups (P=0.30). Among 16 children with CAL, 9 (56%) carried the polymorphism at this locus; among 24 children without CAL, 5 (21%) carried such polymorphism. As for the comparison of two subgroups with and without CAL, the difference in genotype distribution at this locus had statistical significance (P=0.02, OR=4.89, 95% CI: 1.21-19.71).

CONCLUSIONSThe polymorphism of c.212-37insC (rs3832879) in FGF23 gene may not be associated with the pathogenesis of childhood KD, but it may be associated with the development of CAL in children with KD.

Child ; Child, Preschool ; Coronary Artery Disease ; etiology ; genetics ; Female ; Fibroblast Growth Factors ; genetics ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; etiology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic

OBJECTIVEThe minor allele T of rs113420705 (C/T) in caspase-3 gene (CASP3) has been found to significantly increase the risk of Kawasaki disease (KD) and complicate coronary artery lesions (CALs) in Japanese children. In this study, we have explored association of single nucleotide polymorphisms (SNPs) of CASP3 gene and clinic phenotypes of KD.

METHODSA total of 238 unrelated KD patients and 364 healthy controls with matched age, gender and ethnic origins were recruited. Genotypes of the 3 SNPs were determined with PCR-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Allelic, genotypic and haplotypic frequencies were compared between patients and controls, patients with and without CALs, and patients resistant to and responsive to intravenous immunoglobulin (IVIG) treatment.

RESULTSThe T allele and T carriers of rs113420705 were significantly more common in KD patients than controls. A significant difference was also detected in haplotype distribution between patients and controls, where two haplotypes involving the T allele of rs113420705 showed higher frequencies in the patient group. Allelic and genotypic frequencies of the 3 SNPs were similar between patients with and without CALs and those resistant to and responsive to IVIG treatment.

CONCLUSIONOur results suggested that CASP3 probably plays an important role in KD. The T allele of rs113420705 may provide a useful marker for KD susceptibility, although no association between this SNP and clinical prognosis and treatment effect of KD has been found among the selected Chinese children patients.

Caspase 3 ; genetics ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVEKawasaki disease (KD) is a febrile illness of childhood. The etiology of KD remains unknown. Multiple theories exist, including an infectious etiology and an immunological abnormality. Cardiac involvement ranges from myocarditis and pericarditis in the acute stage to the development of coronary artery aneurysms later in the course. The present study aimed to explore the effect of monocyte chemotactic protein-1 (MCP-1) in Kawasaki disease and its relationship with damage to the coronary arteries during the development of KD.

METHODSPlasma MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and MCP-1 mRNA expression in peripheral blood mononuclear cells (PBMC) was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in comparison of three groups: 56 patients with KD, 60 age-matched patients with non-infectious diseases, and 66 age-matched febrile patients with various diseases.

RESULTSPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC of patients with active KD [(409.55 +/- 97.42) pg/ml] and (1.97 +/- 0.77) were higher than those of control group. Plasma MCP-1 levels and MCP-1 mRNA expression of inactive KD group [(301.64 +/- 71.55) pg/ml] and (1.31 +/- 0.39) were significantly higher than those of non-infectious diseases patients. There was a marked increase in patients with inactive KD than those of non-infective patients, but there were no significant differences between inactive KD and febrile patients. Plasma MCP-1 levels and MCP-1 mRNA expression were markedly increased in KD patients with coronary artery lesions than those in patients without coronary artery lesions.

CONCLUSIONPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC were significantly increased in patients with KD, and they were higher in KD with coronary artery lesions. It indicates that MCP-1 may be a useful parameter for monitoring disease activity in patients with KD.

Chemokine CCL2 ; blood ; genetics ; metabolism ; Child ; Child, Preschool ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; genetics ; pathology ; RNA, Messenger ; genetics

OBJECTIVETo study the association of single nucleotide polymorphisms (SNPs, rs223895 and rs223899) in TARC/CCL17 gene with Kawasaki disease (KD) and its clinical characteristics in Han children from Central China.

METHODSA case-control study was performed on 218 children with KD and 248 normal control children. The genotypes of SNPs (rs223895 and rs223899) in TARC/CCL17 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between the SNPs in TARC/CCL17 gene and the clinical characteristics of KD was assessed.

RESULTSThere were significant differences in the genotype (CC, CT, TT) and allele frequencies of SNP rs223895 between children with KD and controls (P<0.05), and C allele was a risk factor (OR=1.397). However, no significant differences were found between the two groups in the genotype and allele frequencies of SNP rs223899. Compared with those with other genotypes (CT+TT) of SNP rs223895, patients with CC genotype had significantly lower hemoglobin (Hb) and albumin (Alb) levels (P<0.05) and a significantly higher erythrocyte sedimentation rate (ESR) (P<0.05).

CONCLUSIONSThe SNP rs223895 in TARC/CCL17 gene is associated with the susceptibility to KD, and C allele is a risk factor. Moreover, SNP rs223895 may influence the levels of Hb, Alb, and ESR.

Chemokine CCL17 ; genetics ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo study the frequency distribution of single nucleotide polymorphisms (SNPs) in two genes associated with incomplete Kawasaki disease (KD) (rs1569723 in CD40 gene and rs2736340 in BLK gene), and to investigate its association with the genetic susceptibility and clinical phenotypes of incomplete KD.

METHODSA total of 184 children with incomplete KD and 203 normal children were recruited to carry out a case-control study. The genotypes of SNPs in CD40 gene and BLK gene were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequency distribution of genotypes was compared between the KD and control groups. The association between gene polymorphisms and clinical features of incomplete KD was analyzed.

RESULTSThere were no significant differences in genotype (AA, AC, CC) and allele frequencies in CD40 SNP rs1569723 between the KD and control groups. There were significant differences in the frequency distribution of three genotypes (TT, CT, CC) in BLK SNP rs2736340 between the KD and control groups (P=0.031), and the KD group had a significantly higher frequency of T allele than the control group (P=0.007). There were significant differences in the incidence of conjunctival hyperaemia among the patients with different genotypes (rs1569723 in CD40 gene) (P=0.036). The SNP rs2736340 in BLK gene was associated with the extremity changes in KD patients (P=0.017).

CONCLUSIONSThe SNP rs2736340 in BLK gene is associated with the susceptibility to incomplete KD, and the SNP rs1569723 in CD40 gene and SNP rs2736340 in BLK gene are associated with some of clinical phenotypes of incomplete KD.

CD40 Antigens ; genetics ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide