Human prostacyclin synthase gene and hypertension : the Suita Study. Export

@article{iwai99, abstract = {BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95\% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.}, author = {Iwai, N. and Katsuya, T. and Ishikawa, K. and Mannami, T. and Ogata, J. and Higaki, J. and Ogihara, T. and Tanabe, T. and Baba, S.}, citeulike-article-id = {1437285}, journal = {Circulation}, keywords = {adult, aged, analysis, ancestry, asian, base, blood, chromosomes, combinedbib, continental, cytochrome, data, diastole, disease, dna, enzyme, factors, female, frequency, gene, genes, genetic, genotype, group, human, humans, hypertension, infarction, intramolecular, japan, male, middle, minisatellite, molecular, multivariate, mutational, myocardial, oxidoreductases, p-450, pair, predisposition, pressure, repeats, reporter, risk, sequence, system, systole, to}, month = {Nov}, number = {22}, pages = {2231--2236}, posted-at = {2007-07-05 14:55:11}, priority = {2}, title = {Human prostacyclin synthase gene and hypertension : the {S}uita {S}tudy.}, volume = {100}, year = {1999} }

TY - JOUR ID - iwai99 L3 - citeulike-article-id:1437285 N2 - BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95\% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population. IS - 22 JF - Circulation EP - 2236 TI - Human prostacyclin synthase gene and hypertension : the {S}uita {S}tudy. VL - 100 SP - 2231 KW - adult KW - aged KW - analysis KW - ancestry KW - asian KW - base KW - blood KW - chromosomes KW - combinedbib KW - continental KW - cytochrome KW - data KW - diastole KW - disease KW - dna KW - enzyme KW - factors KW - female KW - frequency KW - gene KW - genes KW - genetic KW - genotype KW - group KW - human KW - humans KW - hypertension KW - infarction KW - intramolecular KW - japan KW - male KW - middle KW - minisatellite KW - molecular KW - multivariate KW - mutational KW - myocardial KW - oxidoreductases KW - p-450 KW - pair KW - predisposition KW - pressure KW - repeats KW - reporter KW - risk KW - sequence KW - system KW - systole KW - to AU - Iwai, N AU - Katsuya, T AU - Ishikawa, K AU - Mannami, T AU - Ogata, J AU - Higaki, J AU - Ogihara, T AU - Tanabe, T AU - Baba, S PY - 1999/Nov// ER -