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

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

OBJECTIVEThis study examined the expressions of plasma stromal cell derived factor-1 (SDF-1) and CXCR4 mRNA in peripheral blood mononuclear cells (PBMC) of children with Kawasaki disease (KD) and aimed to explore the significance of SDF-1 and CXCR4 mRNA in KD.

METHODSFifty-six children with KD (12 cases complicated by coronary artery lesions) and 60 age and gender-matched healthy children (normal controls) were enrolled in this study. Plasma SDF-1 levels and CXCR4 mRNA expression in PBMC were measured using ELISA and real-time quantitative PCR at the acute and convalescence stages of KD.

RESULTSPlasma SDF-1 levels (1833 +/- 395 ng/L vs 1126 +/- 408 ng/L; P < 0.05) and the CXCR4 mRNA expression in PBMC (6.57 +/- 2.81 vs 2.58 +/- 1.01; P < 0.01) in KD patients were significantly higher than those in normal controls at the acute stage. Both plasma SDF-1 levels and CXCR4 mRNA expression in KD patients decreased significantly at the convalescence stage, but nevertheless remained higher than those in the normal controls. The patients with concomitant coronary artery lesions showed higher CXCR4 mRNA levels than without at the acute stage (8.19 +/- 2.39 vs 6.13 +/- 2.77; P < 0.05).

CONCLUSIONSPlasma SDF-1 concentration and CXCR4 mRNA expression in PBMC increased in KD patients. CXCR4 mRNA might be involved in the development of coronary artery lesions in KD.

Chemokine CXCL12 ; Chemokines, CXC ; blood ; Child, Preschool ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; RNA, Messenger ; blood ; Receptors, CXCR4 ; genetics

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

OBJECTIVETo investigate the expression of myeloid-related protein complex (MRP-8/14) in children with acute Kawasaki Disease (KD).

METHODSA total of 41 children with acute KD and 40 age- and sex-matched control children with upper respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and the number of circulating endothelial cells was determined by flow cytometry.

RESULTSWhen the analysis was stratified according to the presence or absence of coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14 complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of circulating endothelial cells were all significantly higher in KD patients with coronary artery ectasia than in KD patients without coronary artery ectasia (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with the number of endothelial cells in the circulation (r=0.69, P<0.05).

CONCLUSIONSSerum levels of MRP-8/MRP-14 complex are elevated in a positive association with the number of circulating endothelial cells in KD children with coronary artery ectasia, suggesting a causative role in the development of coronary artery lesions.

Acute Disease ; Calgranulin A ; blood ; genetics ; physiology ; Calgranulin B ; blood ; genetics ; physiology ; Child, Preschool ; Coronary Artery Disease ; etiology ; Endothelial Cells ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; pathology ; RNA, Messenger ; analysis

We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.
Alleles ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Interleukin-10/blood/*genetics ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis/*genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Taiwan