Prediction of onset of allergic diseases through analysis of single nucleotide polymorphisms and prevention of onset of allergic diseases by an appropriate intake of flavonoids

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Since the prevalence of allergic diseases has increased dramatically during the last two decades, it is essential to reveal factors that are responsible for the increase and to develop strategies to prevent the onset of allergic diseases.It was found that a novel IL-18 gene polymorphism, IL-18-105A/C was associated with asthma. There was a significant linkage disequilibrium between IL-18-105A/C and IL-18--137G/C which was previously demonstrated to affect IL-18 gene transcription. Moreover, the IL-18 production by purified monocytes in response to LPS or A23187+PMA from volunteers with 105A/A or -137G/G genotype was higher than that with 105A/C or -137G/C genotype, respectively. Therefore, it was suggested that the genetic capacity to produce more IL-18 may have an influence on the onset of asthma.Flavonoids including fisetin, luteolin and apigenin inhibited not only IL-4 and IL-13 synthesis but also CD40 ligand expression by activated basophils. Since at least two signals through IL-4 or IL-13 receptor and through CD40 are required for B cells to differentiate into IgE secreting cells, flavonoids are considered to a natural IgE inhibitor. Luteolin suppressed AP-1 activation without any inhibition of MAPK family by basophils. Furthermore, analyses of inhibitory activity of 45 flavones and related compounds on the IL-4 synthesis by basophils determined a fundamental structure for the inhibition, leading to make a novel flavonoid, that is anticipated to possess high activity and high absorption. Thus this evidence will be helpful for the development of low molecular compounds for allergic diseases and it is expected that a dietary menu including an appropriate intake of flavonoids may provide a form of complementary and alternative medicine and a preventative strategy for allergic diseases. Clinical studies to verify these points are now tested.