RESUMO
We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal control subjects to examine whether these genes would contribute to the KD occurrence and/or the development of coronary artery lesion (CAL) in KD. We found that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism in the promoter region was significantly higher in KD patients with CAL than in those without CAL (p = 0.012) or control subjects (p = 0.021) because of a significantly higher frequency of the GG genotype in KD patients with CAL. In addition, the frequency of the A1 allele with 11 AC repeats of KDR g.+4422(AC)11-14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD patients with CAL than in those without CAL (p = 0.013) or control subjects (p = 0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD with CAL patients. The multivariate analysis of clinical features and genotypes of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14 polymorphism was an independent risk factor for the development of CAL with the highest odds ratio among several clinical parameters (odds ratio 6.76; 95% confidence interval 1.05-43.48). Dual luciferase assay demonstrated that the A1 allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the A2 allele with 12 AC repeats. These findings suggested that VEGF and its receptor, KDR, genes contributed to the development of CAL in KD patients.
Assuntos
Vasos Coronários/patologia , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Fragmento de Restrição , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Criança , Pré-Escolar , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Desequilíbrio de Ligação , Luciferases/genética , Repetições de Microssatélites , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/patologia , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Nitric oxide (NO) is secreted by immune and vascular endothelial cells, and appears to play important roles in the pathophysiology of Kawasaki disease (KD). Thus, genetic variations in NO synthase (NOS) genes may be involved in the development of coronary artery lesions (CAL) in KD. METHODS: The present study investigated the association of endothelial constitutive NOS (ecNOS) and inducible NOS (iNOS) gene polymorphisms with the development of CAL in KD in a Japanese population. RESULTS: The genotype distributions of 27-bp tandem repeat polymorphism within intron 4 of ecNOS gene did not show any significant difference between controls and KD patients with or without CAL. In addition, there was no significant association between whole-allele distribution of iNOS gene promoter (penta-repeat CCTTT) polymorphism and KD with or without CAL. CONCLUSION: These results did not support any association of ecNOS and iNOS gene polymorphisms to the development of CAL in KD patients in a Japanese population.
Assuntos
Povo Asiático/genética , Doença das Coronárias/genética , Síndrome de Linfonodos Mucocutâneos/genética , Óxido Nítrico Sintase/genética , Polimorfismo Genético , Criança , Genótipo , Humanos , Japão , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Sequências de Repetição em TandemRESUMO
UNLABELLED: We investigated the possible use of serum hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels as a predictive indicator for the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41 patients with KD and 25 afebrile controls. Serum HGF levels of patients in the acute phase of KD were significantly higher than those of afebrile controls (Pc < 0.05) and decreased to lower levels during recovery (P < 0.0001). Univariate analysis showed significant correlations between occurrence of CAL and five variables: duration of fever (P=0.018), serum C-reactive protein concentration (P = 0.024), albumin concentration (P=0.009). serum VEGF level (P=0.009) and serum HGF level (P=0.035). Furthermore, multivariate analysis revealed that serum HGF and VEGF levels and presence of oedema were major risk factors for the occurrence of CAL. For prediction of the development of CAL, we established a new risk classification system with these three variables, which showed a sensitivity of 100% and a specificity of 94.4%. CONCLUSION: these data show that hepatocyte growth factor, together with vascular endothelial growth factor, might play an important role in the pathophysiology of Kawasaki disease and their serum levels could be a powerful predictor for the development of coronary artery lesions.
