Pharmacogenetics of asthma in children

Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors

Hypothermia Augments NF-kappaB Activity and the Production of IL-12 and IFN-gamma

Background: The differentiation of Th1 and Th2 is strictly regulated by humoral and cellular factors. The imbalance between Th1 and Th2 is considered to be the pathogenesis of allergic and autoimmune disorders. It is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of Th1 and Th2. Methods: We investigated the expression of IFN-gamma, IL-4, IL-5, IL-10 and IL-12 from LPS- or PHA-stimulated PBMCs at 30°C or 37°C using ELISA and Real-time PCR. We measured the change of NF-kappaB activity at 30°C or 37°C with LPS stimulation using the reporter gene assay. Results: IFN-gamma production from LPS-stimulated PBMCs at 30°C was up-regulated compared with 37°C. IL-5 and IL-10 production from PHA-stimulated PBMCs at 30°C were down-regulated compared with 37°C. This augmented IFN-gamma production was caused by the up-regulation of IL-12 production from CD14+ blood monocytes. Both IL-12 mRNA and IL12 protein at 30°C were up-regulated compared with 37°C. NF-kappaB, the key molecule for the expression of IL-12, was also augmented at 30°C compared with 37°C. Conclusions: Hypothermia up-regulated the expression of IL-12 and IFN-gamma due to the augmented NF-kappaB activity. It is suggested that hypothermia modifies the pattern of cytokine gene expression

Various Expression Patterns of α1 and α2 Genes in IgA Deficiency

Background: IgA deficiency (IgAD) is the most common immunodeficiency, however the pathogenesis in most cases of IgAD is unknown. There are 2 subclasses of IgA, IgA1 and IgA2, and its heavy chains are encoded by 2 different genes, the α1 and α2 genes. To investigate the molecular pathogenesis of IgA deficiency, it is important to evaluate each of the expressions of IgA1 and IgA2 separately. Methods: In this study, we report on the reverse transcriptase (RT)-PCR method in which α1 and α2 mRNAs can be separately evaluated. This method is based on electrophoretic separation using the difference of 39 bases between α1 and α2 mRNAs. Three selective, 5 partial and 2 secondary IgAD patients were examined. Results: In the 3 selective IgAD patients, no α1 or α2 mRNA expression was detected. In the 5 partial IgAD patients, various α1 and α2 mRNA expression patterns were found. One of the partial IgAD patients showed only α2 gene expression, but not α1 gene expression, and was found to show an α1 gene deletion together with γ2 and ε gene deletions. His plasma IgA2 level was within the normal range. Conclusions: Patients with an α1 gene deletion can be considered as having partial IgAD. Using this method, we identified the second case of α1 gene deletion in Japan, and classified IgAD patients on the basis of α1 and α2 expression