Our 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.

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.

Susceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the FcεR1 gene is reportedly associated with atopic asthma in Japanese. To confirm this association, we conducted transmission disequilibrium tests in 76 families identified through atopic asthmatics. A case-control study was also carried out in atopic asthmatic subjects and non-atopic controls. The Gly237 allele was not preferentially transmitted to atopic asthmaaffected offspring. Neither the Gly237 allele nor the Gly237/Gly237 ϩ Glu237/Gly237 genotypes were significantly more prevalent in the atopic asthmatics than in the controls. This study failed to confirm a substantial role of the Gly237Glu polymorphism of the FcεR1 gene in the genetic predisposition for atopic asthma in this Japanese population.

Tumor necrosis factor (TNF) is a proinflammatory cytokine that participates in the inflammatory reaction in patients with asthma. The TNFA and TNFB genes, which encode TNF-alpha and TNF-beta, respectively, are located within the region encoding the human major histocompatibility complex on chromosome 6p21.3, which showed linkage to atopic asthma in our genome-wide search. To determine whether polymorphisms in the 5' flanking region of the TNFA gene (-1031C/T, -863C/A, and -857C/T) and an NcoI polymorphism in the TNFB gene (LTA NcoI) are associated with the development of asthma, we performed transmission disequilibrium tests of families identified through children with atopic asthma. Genotypes of families were determined by polymerase chain reaction-based restriction fragment length polymorphism or SNaPshot analysis. Transmission disequilibrium tests of 144 asthmatic families revealed that transmission of the -857C allele and the -1031T-863C-857C haplotype in the TNFA gene to asthma-affected offspring occurred more frequently than expected (-857C allele, p = 0.0055; -1031T-863C-857C haplotype, p = 0.0002). Our results suggest that TNFA or nearby genes, including those in the major histocompatibility complex region, may contribute to the development of asthma in the Japanese population.

Seasonal allergic rhinitis (SAR) is an inflammatory disease of the nose and eyes that follows

Susceptibility to atopic diseases is known to involve genetic factors. The interleukin-4 (IL-4) receptor- alpha gene (IL4R) reportedly is involved in the development of atopy. A recent study has shown the Ile50 allele of a polymorphism (Ile50Val) of IL4R to be associated with atopy. The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population. We conducted a transmission disequilibrium test in 86 families identified through asthmatic children. A case-control study was also carried out using both atopic and control subjects. The IL4R Ile50Val polymorphism was genotyped by a PCR-restriction fragment length polymorphism method using an intronic upstream primer. The IL4R Ile50 allele was not preferentially transmitted to atopy- or to asthma-affected children. Neither the Ile50 allele nor the Ile50/Ile50 genotype was more prevalent in the atopic subjects than in the control subjects. Our findings indicate that the Ile50Val polymorphism of IL4R does not play a substantial role in genetic predisposition for the etiology of atopy or asthma in this Japanese population.

Our data suggest that cytoplasmic FMRP interacting protein 2 are associated with the development of atopic asthma in humans, and that targeting cytoplasmic FMRP interacting protein 2 could be a novel strategy for treating atopic asthma.

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