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BackgroundSusceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigator have linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5 to atopy and asthma. Recent study has demonstrated that the T allele of a polymorphism in the IL-4 gene promoter region (C-590T) is associated with elevated levels of total serum IgE. ObjectiveThe objective of this study was to evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the allergic response and asthma in Japanese children. Method and ResultsThe study was conducted in two different populations: families ascertained through asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and atopy to chromosome 5q31–33 is suggested and a random general population (control group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR-restriction fragment length polymorphism analysis. Frequency of the T allele was 0.73 in the asthmatic group and 0.70 in the control group. No significant difference in the levels of total serum IgE and specific IgE to house dust mite was observed between subjects with homozygote for the C allele, a heterozygote and a homozygote for the T allele by intrafamilial and interfamilial comparisons. Using the transmission disequilibrium test, however, we found a significantly frequent transmission of the T allele to asthmatic children (χ2 = 5.72, P = 0.023). ConclusionOur data suggest that the IL-4 promoter C-590T polymorphism may be associated with the development of asthma in Japanese children, but not through modulating total serum IgE levels. [ABSTRACT FROM AUTHOR]

Background Prostaglandin D2 (PGD2 ), a major cyclo-oxygenase metabolite of arachidonic acid in mast cells, induces bronchoconstriction in the human lung. It has been reported that mice lacking PGD receptor fail to develop the bronchial hyper-responsiveness upon ovalbumin challenge, suggesting that PGD2 functions as a mediator of allergic asthma. Objective To determine if there are any mutations associated with the development of asthma in the haematopoietic prostaglandin D synthase (H-PGDS) gene and the human prostanoid DP receptor (PTGDR) gene. Methods and results We screened the 5′flanking and coding regions of the H-PGDS gene and the PTGDR gene by direct sequence. We identified one variant in intron 2 (IVS2 + 11 A > C) and one variant in intron 3 (IVS3 + 13T > C) of the H-PGDS gene, and two variants in the 5′flanking region of the PTGDR gene (-197T > C and -2C > T). The IVS3 + 13T > C and -197T > C variants were rare, appearing only once in 48 subjects. transmission disequilibrium test (TDT) analysis of 144 asthmatic families revealed that the IVS2 + 11 A allele of the H-PGDS gene was significantly transmitted preferentially to asthma-affected children (P = 0.0056), but no association was observed between -2C/T polymorphism of the PTGDR gene and asthma (P > 0.05). Conclusion Our results suggest that the IVS2 + 11 A/C allele may be involved in the development of asthma in the Japanese population. [ABSTRACT FROM AUTHOR]