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Background: Previous research demonstrated the association between cyclooxygenase-2 (COX-2) gene polymorphisms and susceptibility to Kawasaki disease (KD). This study aims to detect the plasma concentration of COX-2 in different phases of KD patients and evaluate the relationship between COX-2 level and coronary artery lesion formation, therapeutic response to intravenous immunoglobulin. Methods: Plasma COX-2 levels were measured by enzyme-linked immunosorbent assay in KD patients during the acute (a-KD, n  = 52), subacute (s-KD, n  = 46), and convalescent (c-KD, n  = 43) phase. Results: The concentration of COX-2 in the a-KD group was significantly higher than that in the s-KD, c-KD, healthy control or febrile control group, respectively. There was no difference in the levels of COX-2 between the KD with or without coronary artery lesion subgroups, intravenous immunoglobulin resistant, and sensitive subgroups in the a-KD group, respectively. Conclusions: The plasma concentration of COX-2 might be a novel potential biomarker of acute KD.

Objectives: Kawasaki disease (KD) is the most common autoimmune vasculitis syndrome in children, which supposed be a complex polygenic disorder. Interleukin-17 (IL-17) is a member of the pro-inflammatory cytokine family, which has a strong pro-inflammatory effect and can participate in various acute and chronic inflammatory responses. This study aims to investigate the relationship between the single-nucleotide polymorphism (SNP) locus rs3819025 in the IL-17A gene and the susceptibility to KD., Methods: A total of 120 patients with KD who met the diagnostic criteria (the KD group) and 120 healthy children (the control group) were enrolled retrospectively in this study. Polymerase chain reaction (PCR) and DNA direct sequencing were used to detect the SNPs of children in the 2 groups., Results: The frequencies of GG, GA, and AA genotypes of rs3819025 locus in the IL-17A gene in the KD group were 82.5%, 17.5%, and 0, respectively, and the frequencies of GG, GA, and AA genotypes in the control group were 72.5%, 22.5%, and 5.0%, respectively. There were significant differences in both genotype ( χ 2 =7.524, P =0.023). The allele frequencies G and A of rs3819025 locus in the KD group were 91.25% and 8.75%, respectively, while those in the control group were 83.75% and 16.25%, respectively. There was significant difference between the 2 groups ( χ 2 =6.171, P =0.013). The distribution frequencies of GG or GA genotype and G or A allele were 88.46% or 11.54% and 94.23% or 5.77% in the KD group with coronary artery lesion, respectively. The distribution frequencies of GG or GA genotype and G or A allele were 78.72% or 21.28% and 89 . 36% or 10.64% in the KD group without coronary artery lesion, respectively. There were no significant differences in genotype and allele frequencies of rs3819025 between the KD with coronary artery lesion group and the KD group without coronary artery lesion (both P >0.05). Besides, children with the allele A had a 2.023 times higher risk of KD than those without the allele A ( χ 2 =6.171, P =0.013; OR =2.023, 95% CI 1.151 to 3.557)., Conclusions: The locus rs3819025 in the IL-17A gene is associated with the pathogenesis of KD. The allele A of the locus rs3819025 in the IL-17A gene may be a risk factor for KD.

Kawasaki disease (KD)), also known as mucocutaneous lymph node syndrome (MCLS), is an autoimmune and systemic vasculitis syndrome. Its etiology and pathogenesis are still unclear. microRNAs (miRNA), a novel class of small non-coding RNAs, regulate the expression of multiple protein-encoding genes at the post-transcriptional level. We intend to study the change of miRNA-133a in the plasma of patients with KD, explore the role of miRNA-133a on HUVEC and define the pathogenesis of vascular dysfunction in KD. miRNA-133a expression and the mRNA and protein expression of protein phosphatase 2 catalytic subunit alpha (PPP2CA) were assessed by RT-qPCR and Western blot, respectively. The PPP2CA mRNA 3'UTR was predicted to be the potential target of miRNA-133a by using the miRNA databases and verified by the luciferase assay. The plasmids of miRNA-133a mimics and inhibitors were transfected into HUVEC cells. The plasma soluble vascular endothelial cadherin (sVE-cadherin, the excised extracellular part of VE-cadherin) levels were investigated by ELISA. The results suggested that miRNA-133a was increased by 3.8 times in the acute KD group and by 2.7 times in the convalescent KD group compared with the control group (both P =  .000). PPP2CA is the target gene of miRNA-133a and its expression was inhibited by miRNA-133a acting on PPP2CA mRNA 3'UTR ( P =  .013). The plasma sVE-cadherin levels in the acute KD groups were increased compared with the control group ( P =  .024). The ROC curve analysis showed that the expression of miRNA-133a segregate acute KD patients from convalescent KD patients and healthy children. Our results suggest that miRNA-133a might be a new biomarker for KD.

Background: Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility., Methods: This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing., Results: There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371-0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05)., Conclusion: This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease.

Background : Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Cyclophilin A (CypA), also known as PPIA , has been identified to play a vital role in the pathogenesis of cardiovascular or inflammatory diseases. However, no studies have examined the relationship between single-nucleotide polymorphisms (SNPs) in the peptidylprolyl isomerase A ( PPIA ) and the development of KD and KD with or without coronary artery lesions (CALs). Objective : The present study was conducted to evaluate whether PPIA SNPs are associated with susceptibility to KD or CALs in KD. Methods : Three PPIA SNPs were genotyped in 101 KD patients and 105 healthy controls from a Chinese population. The allele and genotype frequencies were compared between the case and control groups, as well as in KD patients with and without CALs. Results : The data revealed a significant difference in the genotype and allele frequencies of rs17860041 A/C between KD patients and normal controls. Compared to the rs17860041 CC genotype, the AC genotype demonstrated a consistently beneficial roles in reducing the KD incidence. Furthermore, the allele frequency of C in the KD group was higher than that in the control group ( P <  .05). Haplotype analysis for PPIA polymorphisms (rs10951772 A/G, rs17860041 A/C, and rs4720485 A/T) also confirmed this association in KD patients and normal controls. Conclusion : A PPIA promoter SNP (rs17860041 A/C) confers susceptibility to KD in Chinese children and was identified as an important marker of KD in this study.

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 ( P <0.001, P =0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children ( P =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.

Objective: To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children.
 Methods: A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited. Seven tagging SNPs (rs6088738, rs2069940, rs2069945, rs2069952, rs867186, rs9574, and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay. The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA.
 Results: We found a significant association between rs2069952, rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation. Interestingly, males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females. The level of plasma sEPCR in children with KD didnot predict the formation of CAL. However, the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients.
 Conclusion: The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.

Objective: To investigate the genetic association of miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with Kawasaki disease (KD) and coronary artery lesions (CAL)., Methods: There were 120 patients with KD and 126 healthy subjects in this study. The genotype of loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected by polymerase chain reaction-sequence-based typing., Results: For miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there were no significant difference of genotype frequencies and allele frequencies between KD group and healthy control group, or between the IVIG-resistant group and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL) group, the genotype frequencies of GG were higher than that in KD without coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR-146a gene (χ 2  = 6.660, P = 0.036), patients with KD carried genotype of GG were at 3.636 times higher risk of getting coronary artery lesions than those of non-carriers (χ 2  = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280-10.262). While there was no significant difference of allele frequency of G and C between KD-CAL group and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene (χ 2  = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk of getting coronary artery lesions than those of non-carriers (χ 2  = 4.745, P = 0.035, OR = 2.422, 95%CI = 1.073-5.465), while there was no significant difference of genotype frequency of AA, AG, and GG types between KD-CAL group and KD-WO group (P > 0.05). There was no significant difference of genotype frequencies of TT, TC, and CC types and allele frequencies of T and C types between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR-146a gene (P > 0.05)., Conclusions: The significant association has been found between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329 A/G were risk factors for getting coronary artery lesions.

Background: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children, and it can result in coronary artery lesions. Cyclooxygenase-2 (COX-2) is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of several prostaglandins. The aim of this study was to examine the association between COX-2 gene polymorphisms and susceptibility to KD., Methods: A total of 276 subjects (136 KD and 140 controls) were recruited. The analysis of two single nucleotide polymorphisms rs689466 (-1195G/A) and rs20417 (-765G/C) was respectively detected with polymerase chain reaction sequence-based typing methods., Results: Polymorphisms of rs689466 were significantly different between the normal controls and KD patients (χ 2  = 6.070 and 5.435, both p < 0.05). The frequencies of AA genotype and A allele of rs689466 in Kawasaki disease group were higher than that of control group (χ 2  = 4.832, p = 0.028, OR = 1.832, 95%CI = 1.064-3.124; χ 2  = 5.435, p = 0.028, OR = 1.491, 95%CI = 1.065-2.088)., Conclusion: This study provides the first evidence supporting an association between COX-2 gene polymorphisms and susceptibility of KD. The AA genotype and A allele of rs689466 confer predisposing factors to KD.

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children and can result in coronary artery lesions (CALs). Thrombomodulin (TM) is a critical cofactor in the protein C anticoagulant system. The TM C1418T (rs1042579) polymorphism is associated with a high risk of cardiac-cerebral vascular diseases. But the association of the TM C1418T polymorphism with susceptibility to KD, CAL formation, and intravenous immunoglobulin (IVIG) resistance is still unclear. In our study, we examined the TM C1418T polymorphism in 122 children with KD and 126 healthy children and revealed the correlation between the TM C1418T polymorphism and KD, CAL formation, and IVIG resistance.

Background: Kawasaki disease (KD) is a childhood systemic vasculitis that exhibits a specific preference for the coronary arteries. The aetiology remains unknown and there are no especially diagnostic tests. microRNAs (miRNAs) are 18 to 23 nucleotides non-coding RNAs that are negative regulator of gene expression and play a crucial role in the regulatory network of the genome. Recently, circulating miRNAs have been found presentation in human plasma and displayed some characteristics of the ideal biomarker. However, few researches explored differentially expressed miRNAs in the plasma of KD patients. Our study is to identify circulating miRNAs in KD plasma which can serve as potential biomarkers of KD diagnosis., Materials and Methods: The total of five pairs of acute KD and normal plasma samples were analyzed using ABI miRNAs TLDA Assay chip. Differentially expression of miR-125a-5p in plasma were confirmed by quantitative real-time PCR (qRT-PCR) in independent cohort (acute KD = 30, convalescent KD = 30 and healthy control = 32). After bioinformatics prediction, miR-125a-5p vector and inhibitor were transfected into HUVECs respectively, to observe MKK7 expression as a potential target gene. Flow cytometry was used to analyze apoptosis. The mRNA and protein levels of desired genes including MKK7, Caspase-3, Bax and Bcl2 were detected by qRT-PCR and western blotting., Results: Eighteen miRNAs were differentially expressed in acute KD's plasma compared with healthy control. miR-125a-5p was significantly increased in plasma of KD patients (p = 0.000), but no variation between acute and convalescent KD (p = 0.357). Moreover, the results from the gain and loss functions of miR-125a-5p in HUVECs have shown that miR-125a-5p remarkably suppressed MKK7 expression, as a novel target gene. Importantly, miR-125a-5p also induced apoptosis in HUVECs through inhibition MKK7 levels to regulate Bax/Bcl2 pathway resulting to activate Caspase-3., Conclusion: Our study indicated that the circulating miR-125a-5p levels in KD's plasma have remarkably evaluated compared with healthy individuals. miR-125a-5p might play a role in the development of KD by regulating target gene MKK7 to induce apoptosis in vascular endothelial cells. Therefore, our findings have suggested that detected miR-125a-5p levels in plasma could be used as a potential biomarker in early KD diagnosis.

Objective: To explore the correlation between the -31T/C polymorphisms of IL-1β gene and thesusceptibility of Kawasaki disease (KD).
 Methods: The polymorphism at -31C/T site of IL-1β gene was genotyped with the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 100 KD patients (KD group) and 100 healthy children (control group). The differences in genotype distribution and allele frequency between the KD group and the control group were analyzed by χ2 test.
 Results: There were significant differences in genotype and allele frequencies for IL-1β gene polymorphism at -31C/T site between the KD group and the control group (all P<0.05). The risk of KD in the KD group with TT genotype was 0.37 times as that with the CT and CC genotypes (χ2=5.65, P<0.005, OR=0.37, 95%CI 0.16 to 0.85). But there was no significant difference in genotype and allele frequencies for IL-1β genepolymorphism at -31 site between the KD group with coronary artery lesion and the KD group without coronary artery lesion(all P>0.05).
 Conclusion: The polymorphism at -31T/C site of IL-1β gene is associated with genetic susceptibility of KD. The KD patients with TT genotype are at low risk.

Kawasaki disease (KD) is an acute systemic vasculitis complicated by development of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which plays an important role in coronary artery disease. The relationship between PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD patients and 59 healthy children and revealed the correlation of PECAM-1 gene polymorphisms in KD children with and without coronary artery lesions (CAL).