Yukako Yokouchi

A genome-wide linkage analysis of orchard grass- sensitive childhood seasonal allergic rhinitis in Japanese families

Seasonal allergic rhinitis (SAR) is an inflammatory disease of the nose and eyes that follows sensitization to air-born pollens. We conducted a genome-wide linkage screening of 48 Japanese families (188 members) with orchard grass (OG)-sensitive SAR children (67 affected sib-pairs) in a farming community in central Japan where OG was planted for apple farming and OG pollen is a major cause of SAR. We used the GENEHUNTER program to performed nonparametric multipoint linkage analysis for OG-sensitive SAR as a qualitative trait and for log total serum IgE levels and OG-RAST IgE levels as quantitative traits. Genotyping data of 400 microsatellite markers suggested linkage of SAR to chromosomes 1p36.2, 4q13.3, and 9q34.3 (P < 0.001), linkage of serum total IgE levels to 3p24.1, 5q33.1, 12p13.1, and 12q24.2 (P < 0.001), and linkage of OG-RAST IgE levels to 4p16.1, 11q14.3, and 16p12.3 (P < 0.001). Weak evidence for linkage of SAR to 5q33.1 was also observed (P = 0.01). All these regions, with the exception of 9q34.3, have been previously reported to be linked to asthma and/or atopy. These data suggest that, although loci linked to SAR are likely to be common to asthma, a strong contribution by specific gene(s) to OG-sensitive SAR is unlikely.

Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese.

Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin‐4 (IL‐4) receptor α gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL‐4 receptor α chain gene (Q576R) to be associated with atopy.

Identification of missense mutation in the IL12B gene: lack of association between IL12B polymorphisms and asthma and allergic rhinitis in the Japanese population.

Interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and can suppress allergic inflammation. In a genome-wide screen, we found strong evidence for linkage of atopic asthma with marker D5S1352, located close to IL12B, with a maximum lod score of 4.34. We screened for mutation in IL12B and found three novel (-4475–4insG, Glu186Asp and Ser226Asn) variants and one previously reported (1188A>C) variant in IL12B, and conducted transmission disequilibrium tests in families identified through children with atopic asthma or allergic rhinitis. Frequencies of the Asn226 and 1188C alleles in the parents were 0.04 and 0.5, respectively. Preferential transmission of either the Ser226/Asn226 or 1188A/C allele to asthma-affected or rhinitis-affected children was not observed (P > 0.1) and was not associated significantly with total serum IgE level (P > 0.1). Our results indicate that polymorphisms in IL12B are not likely to be associated with the development of atopy-related phenotypes.

New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes

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.

No association between atopic asthma and a coding variant of FcεR1β in a Japanese population

AbstractSusceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the FcεR1β 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 asthma-affected offspring. Neither the Gly237 allele nor the Gly237/Gly237 + 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 FcεR1β gene in the genetic predisposition for atopic asthma in this Japanese population.

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

IL‐4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL‐4 gene cluster and asthma and/or asthma‐related traits. Interferon regulatory factor 1 (IRF‐1) is located approximately 300 kb telomeric to IL‐4 and recent study reveals that IRF‐1 deficiency results in an elevated production of Th2‐related cytokines and a compensatory decrease in the expression of native cell‐ and Th1‐related cytokines.