Polymorphism of the promoter region of prostacyclin synthase gene in chronic thromboembolic pulmonary hypertension.
OBJECTIVE
Decreased expression of prostacyclin synthase (PGIS) is observed in the lung vasculature of patients with pulmonary arterial hypertension and the biosynthesis of prostacyclin (PGI2) may be impaired in chronic thromboembolic pulmonary hypertension (CTEPH). Whether it is genetically determined or develops as the disease progresses is unclear. A variable-number tandem repeat (VNTR) polymorphism has been detected in the 5'-upstream promoter region of the PGIS gene. It has been demonstrated that the alleles vary in size from three to seven repeats of nine base pairs, and transcriptional activity increased with the number of repeats. The purpose of the present study was to elucidate the association between the VNTR polymorphisms of the PGIS gene and CTEPH in Japanese subjects.


METHODS
Ninety patients with CTEPH and 144 control subjects were investigated for the presence of VNTR polymorphisms. Sixty-two blood samples were obtained from CTEPH patients and the plasma concentrations of prostacyclin and thromboxane A2 metabolites were measured.


RESULTS
VNTR polymorphisms in the prostacyclin synthase gene were grouped into L alleles (five, six and seven repeats) and S alleles (three and four repeats). The overall distribution of the alleles and genotypes were not significantly different between CTEPH patients and the control subjects. The patients with the LL genotype had higher plasma concentrations of 6-keto-prostaglandin F1alpha than patients with the LS and SS genotypes.


CONCLUSIONS
Our results suggested that the specific VNTR polymorphism in the 5'-upstream promoter region of the PGIS gene regulated prostacyclin production, but did not seem to be associated with the development of CTEPH in this patient population.
Amano
Shinya
S
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Tatsumi
Koichiro
K
Tanabe
Nobuhiro
N
Kasahara
Yasunori
Y
Kurosu
Katsushi
K
Takiguchi
Yuichi
Y
Kasuya
Yoshitoshi
Y
Kimura
Sadao
S
Kuriyama
Takayuki
T
D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011655:Pulmonary Embolism / Q000150:complications; D013928:Thromboxane A2 / Q000235:genetics
D013928:Thromboxane A2; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase