Human prostacyclin synthase gene and hypertension : the Suita Study.
Human prostacyclin synthase gene and hypertension : the Suita Study.
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人前列环素合酶基因与高血压：吹田研究。
DOI：
10.1161/01.cir.100.22.2231
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发表时间：
1999
期刊：
影响因子：
37.8
通讯作者：
S. Baba
中科院分区：
文献类型：
--
作者：
Naoharu Iwai;T. Katsuya;K. Ishikawa;T. Mannami;J. Ogata;J. Higaki;T. Ogihara;Tadashi Tanabe;S. Baba
背景
前列环素（前列腺素I（2））是一种强血管扩张剂，可抑制血管平滑肌细胞的生长，也是血小板聚集的最有效的内源性抑制剂。因此，它被认为在心血管疾病中发挥重要作用。基于前列环素合酶基因的变异在人类心血管疾病中也可能发挥重要作用的假设，我们对人类前列环素合酶基因的变异进行了筛选。
方法和结果
我们已经检测到在人类前列环素合酶基因的启动子区的重复多态性。9 bp（CCGCCAGCC）的启动子区，编码一个串联重复的Sp1转录结合位点的重复序列的数量在3和7之间变化，在日本受试者。荧光素酶报告基因分析表明，3和4个重复的等位基因（R3和R4，分别）在培养的人脐静脉内皮细胞启动子活性较低。然后，我们调查了这种重复多态性与血压在一个大的人口为基础的样本（Suita研究），其中包括4971名日本参与者的可能关联。多变量模型显示，R3 R3、R3 R4或R4 R4基因型（SS基因型，n=80）的参与者具有显著较高的收缩压（P=0.0133）和脉压（P=0.0005）。SS基因型高血压（140/90 mm Hg）的优势比为1.942（95%可信区间3.20至1.19，P=0.0084）。
结论
人前列环素合酶基因的重复多态性似乎是高脉压的危险因素，因此也是日本人群收缩期高血压的危险因素。
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.
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类二十烷酸调节动脉平滑肌细胞表型、增殖能力和胆固醇代谢。
DOI：
10.1161/01.atv.9.4.413
发表时间：
1989
期刊：
Arteriosclerosis (Dallas, Tex.)
影响因子：
--
作者：
Pomerantz,KB;Hajjar,DP
通讯作者：
Hajjar,DP
影响因子：
158.5
作者：
FITZGERALD, GA;SMITH, B;BRASH, AR
通讯作者：
BRASH, AR
影响因子：
37.8
作者：
S. Franklin;William Gustin;N. Wong;M. Larson;M. Weber;W. Kannel;Daniel Levy
通讯作者：
S. Franklin;William Gustin;N. Wong;M. Larson;M. Weber;W. Kannel;Daniel Levy
影响因子：
37.8
作者：
FITZGERALD, DJ;ENTMAN, SS;FITZGERALD, GA
通讯作者：
FITZGERALD, GA