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 + 11A/C allele may be involved in the development of asthma in the Japanese population.
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 + 11A/C allele may be involved in the development of asthma in the Japanese population.
Authors: Brigette L Tippin; A Joan Levine; Alicia M Materi; Wen-Liang Song; Temitope O Keku; Julie E Goodman; Leah B Sansbury; Sudipto Das; Aihua Dai; Alan M Kwong; Amy M Lin; John M Lin; Jae Man Park; Ruth E Patterson; Rowan T Chlebowski; R Michael Garavito; Tsuyoshi Inoue; Wonhwa Cho; John A Lawson; Shiv Kapoor; Laurence N Kolonel; Loïc Le Marchand; Robert W Haile; Robert S Sandler; Henry J Lin Journal: Prostaglandins Other Lipid Mediat Date: 2011-07-28 Impact factor: 3.072