OBJECTIVE: To study the association of the polymorphisms of the serum amyloid A1 (SAA1) gene at rs4638289 and rs7131332 loci with Kawasaki disease (KD) and its complication coronary artery lesion (CAL) in children. METHODS: A total of 105 Han children with KD who were hospitalized and treated from 2013 to 2017 were enrolled as the KD group. A total of 100 Han children who underwent physical examination were enrolled as the control group. According to the presence or absence of CAL, the KD group was further divided into a CAL group with 23 children and a non-CAL (NCAL) group with 82 children. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the polymorphisms of the SAA1 gene at rs4638289 and rs7131332 loci. RESUKTS: For the locus rs4638289 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AT, and TT and the allele frequencies of A and T (P>0.05). But there were significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AT, and TT (P=0.016), while there were no significant differences in the allele frequencies of A and T (P>0.05). AT genotype was a protective factor against CAL (OR=0.276, 95%CI: 0.099-0.772, P=0.011). For the locus rs7131332 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). There were also no significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). CONCLUSIONS Polymorphisms of the SAA1 gene at loci rs4638289 and rs7131332 are not associated with the onset of KD, while the polymorphism at the locus rs4638289 is associated with CAL in KD patients. KD patients with genotype AT may have a reduced risk of CAL.
Case-Control Studies ; Child ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Serum Amyloid A Protein ; 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

OBJECTIVETo investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms and its association with the development of Kawasaki disease and coronary artery lesion (CAL).

METHODSA total of 81 children with Kawasaki disease (among whom 11 had CAL) and 100 normal children who underwent physical examination (control group) were enrolled in a case-control study. Sequencing was performed to investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms.

RESULTSThere were no significant differences between the Kawasaki disease and control groups in the frequencies of TT, TG, and GG genotypes and T/G alleles of +45T/G polymorphism in the adiponectin gene (P>0.05). In the Kawasaki disease group, there were also no significant differences in the genotype and allele frequencies of the +45T/G polymorphism between the children with CAL and those without (P>0.05). There were significant differences between the Kawasaki disease and control groups in the frequencies of GG, GT, and TT genotypes and G/T alleles of +276G/T polymorphism in the adiponectin gene (P<0.05). GG genotype was a risk factor for the development of Kawasaki disease (OR=2.313, P=0.006). In the Kawasaki disease group, there was no significant difference in the genotype distribution of the +276G/T polymorphism between the children with CAL and those without (P>0.05).

CONCLUSIONSThe adiponectin +276G/T polymorphism may be associated with the development of Kawasaki disease, but not associated with CAL. The adiponectin +45T/G polymorphism may not be associated with Kawasaki disease or CAL.

Adiponectin ; genetics ; Case-Control Studies ; Child ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide

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

PURPOSE: Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guérin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans. MATERIALS AND METHODS: Associations between KD and SNPs in two genes were evaluated. Potential associations between BCG injection site erythema and SNPs in two genes were also evaluated. Gene-gene interactions between ITPKC and SLC11A1 in KD and BCG injection site erythema were also analyzed. RESULTS: Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1 were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG injection site erythema. CONCLUSION: This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants identified in this study affected KD and erythema of BCG injection sites independently and through gene-gene interactions. Also, the effects of the polymorphisms were age-dependent.
Asian Continental Ancestry Group/genetics ; BCG Vaccine/administration & dosage ; Case-Control Studies ; Cation Transport Proteins/genetics ; Child ; Child, Preschool ; Epistasis, Genetic ; Erythema/complications ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome/genetics ; Mutation Rate ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Polymorphism, Single Nucleotide/genetics ; Republic of Korea

OBJECTIVE: The etiology of the Kawasaki disease (KD) remains unknown despite of extensive studies but infection, immunity, and genetics were suggested as causes. There have been attempted to link susceptibility to KD to allelic variations to search related gene. The enabled homolog (Enah) gene on the human chromosome 1q42.12 encodes enabled/vasodilator-stimulated phosphoprotein (Ena/VASP). Ena/VASP is a regulator of actin cytoskeleton, exists in cytoplasm, and maintains homeostasis such as immune response, blood vessel preservation, and hemostasis. The aim of this study was to investigate polymorphisms of the Enah gene as a risk factor for KD and coronary artery lesions (CALs) as a complication. METHODS: In the Enah gene region, 15 single nucleotide polymorphisms (SNPs) were selected using human SNP websites (http://www.hapmap.org/, genome build). Three hundred and six healthy controls and 106 KD subjects were recruited. SNP genotyping was performed using the Golden Gate assay on an Illumina BeadStation 500 GX (Illumina Inc., San Diego, CA, USA). Frequencies of allele were obtained and the genetic association between of the Enah gene polymorphisms and susceptibility to KD and CALs was analyzed by SNPstats, Haploview software ver. 4.1 (Broad Institute, Cambridge, MA, USA). Multiple logistic regression analysis with adjustment for gender was performed. RESULTS: One SNP (rs1891000) among total fifteen SNPs was associated with KD. Moreover, we found a significant association between rs487591, rs576861, rs7555139, rs10799319, and the development of CALs in KD patients. CONCLUSION: These results suggest that the polymorphism of Enah gene may be associated with the occurrence of KD and development of CALs as a complication.
Actin Cytoskeleton ; Alleles ; Blood Vessels ; Child* ; Chromosomes, Human ; Coronary Vessels ; Cytoplasm ; Genetics ; Genome ; Hemostasis ; Homeostasis ; Humans ; Logistic Models ; Mucocutaneous Lymph Node Syndrome* ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVETo study the role of triggering receptor expressed on myeloid cells-1(TREM-1) in the pathogenesis of Kawasaki disease (KD).

METHODSBased on color Doppler examination results, 45 children with KD were classified into two groups: coronary artery lesions (CAL group) and no coronary artery lesions (NCAL group). Fifteen children with fever caused by respiratory infection (fever control group) and fifteen healthy children (normal control group) served as controls. Real-time fluorescence quantitative PCR was used to detect the expression of TREM-1 mRNA and DNAX-activating protein 12 (DAP12) mRNA in peripheral blood mononuclear cells (PBMC). ELISA was used to detect the expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), DAP12, monocyte chemoattractant protein-1(MCP-1), interleukin-8 (IL-8) proteins levels.

RESULTSThe mean serum protein concentrations of sTREM-1 and DAP12 and the expression levels of TREM-1 mRNA and DAP12 mRNA in PBMC in 45 children with KD (KD group) were significantly higher than in the two control groups (P<0.05). The levels of sTREM-1 protein and TREM-1 mRNA in the CAL subgroup were significantly higher than in the NCAL subgroup (P<0.05). The serum protein concentrations of MCP-1 and IL-8 in the KD group were significantly higher than in the two control groups (P<0.05). The MCP-1 protein level in the CAL subgroup was significantly higher than in the NCAL subgroup (P<0.05). In children with KD, there was a positive correlation between serum sTREM-1 and MCP-1 levels (r=0.523, P<0.05).

CONCLUSIONSTREM-1 activation may be involved in the development of KD.

Chemokine CCL2 ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-8 ; blood ; Male ; Membrane Glycoproteins ; blood ; genetics ; physiology ; Mucocutaneous Lymph Node Syndrome ; etiology ; immunology ; RNA, Messenger ; analysis ; Receptors, Immunologic ; blood ; genetics ; physiology ; Triggering Receptor Expressed on Myeloid Cells-1

In order to perform large-scale genetic studies of Kawasaki disease (KD) in Korea, the Korean Kawasaki Disease Genetics Consortium (KKDGC) was formed in 2008 with 10 hospitals. Since the establishment of KKDGC, there has been a collection of clinical data from a total of 1198 patients, and approximately 5 mL of blood samples per patient (for genomic deoxyribonucleic acid and plasma isolation), using a standard clinical data collection form and a nation-wide networking system for blood sample pick-up. In the clinical risk factor analysis using the collected clinical data of 478 KD patients, it was found that incomplete KD type, intravenous immunoglobulin (IVIG) non-responsiveness, and long febrile days are major risk factors for coronary artery lesions development, whereas low serum albumin concentration is an independent risk factor for IVIG non-responsiveness. In addition, we identified a KD susceptibility locus at 1p31, a coronary artery aneurysm locus (KCNN2 gene), and the causal variant in the C-reactive protein (CRP) promoter region, as determining the increased CRP levels in KD patients, by means of genome-wide association studies. Currently, this consortium is continually collecting more clinical data and genomic samples to identify the clinical and genetic risk factors via a single nucleotide polymorphism chip and exome sequencing, as well as collaborating with several international KD genetics teams. The consortium-based approach for genetic studies of KD in Korea will be a very effective way to understand the unknown etiology and causal mechanism of KD, which may be affected by multiple genes and environmental factors.
Aneurysm ; C-Reactive Protein ; Coronary Vessels ; Data Collection ; DNA ; Exome ; Genetics* ; Genome-Wide Association Study ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Korea* ; Mucocutaneous Lymph Node Syndrome* ; Plasma ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors ; Serum Albumin

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