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.


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.


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).


CONCLUSIONS
Our results suggest that the IVS2 + 11A/C allele may be involved in the development of asthma in the Japanese population.
Noguchi
E
E
Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba City, Japan. mo00f210@md.tsukuba.ac.jp
Shibasaki
M
M
Kamioka
M
M
Yokouchi
Y
Y
Yamakawa-Kobayashi
K
K
Hamaguchi
H
H
Matsui
A
A
Arinami
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001249:Asthma / Q000209:etiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007438:Introns / Q000235:genetics; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000235:genetics*
D054834:Lipocalins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C036293:prostaglandin D2 receptor