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New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes
Author(s) -
Noguchi E.,
Shibasaki M.,
Kamioka M.,
Yokouchi Y.,
YamakawaKobayashi K.,
Hamaguchi H.,
Matsui A.,
Arinami T.
Publication year - 2002
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.0022-0477.2001.01261.x
Subject(s) - prostaglandin d2 , allele , intron , gene , biology , population , prostanoid , microbiology and biotechnology , immunology , receptor , genetics , medicine , environmental health
Background Prostaglandin D 2 (PGD 2 ), 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 PGD 2 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.