ABSTRACT
Interleukin-12 (IL-12) secreted from macrophages or dendritic cells plays an important role in the protection against intracellular pathogens as well as the developmental commitment of T helper 1 cells. IL-12 exerts its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12Rbeta1 and IL 12Rbeta2. In this paper, we performed association studies between the three reported polymorphisms (Q214R, M365T and G378R) of the IL-12Rbeta1 gene or the newly identified polymorphisms (P238L, IVS9 -7G>A, IVS13 -121G>A, A643T, P779P and c.3283T>G) of the IL-12Rbeta2 gene, and the development of type 1 diabetes or atopic asthma as representative Th1- and Th2- dominant diseases, respectively. The association study of each polymorphism of the IL-12Rbeta1 or IL-12Rbeta2 gene and type 1 diabetes or asthma showed that these IL-12R genes did not contribute to the development of type 1 diabetes or asthma in the Japanese population. Further analysis in individuals with susceptibility to intracellular pathogens may elucidate the importance of the IL-12R genes.
Subject(s)
Asthma/genetics , Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , Receptors, Interleukin/genetics , Adolescent , Asthma/etiology , Child , Child, Preschool , Diabetes Mellitus, Type 1/etiology , Humans , Infant , Infant, Newborn , Interferon-gamma/metabolism , Japan , Polymorphism, Single Nucleotide , Receptors, Interleukin/metabolism , Receptors, Interleukin-12ABSTRACT
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.
