Clinical & Experimental Allergy

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

Authors


Emiko Noguchi, Department of Medical Genetics, Institute of Basic Medical SciencesUniversity of Tsukuba, 1-1-1 Tennoudai Tsukuba, Ibaraki-ken, 305–8575, Japan. E-mail: mo00f210@md.tsukuba. ac.jp

Abstract

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.

Ancillary