Polymorphism of the promoter region of prostacyclin synthase gene in chronic thromboembolic pulmonary hypertension
Polymorphism of the promoter region of prostacyclin synthase gene in chronic thromboembolic pulmonary hypertension
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DOI：
10.1111/j.1440-1843.2004.00568.x
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发表时间：
2004-06-01
期刊：
影响因子：
6.9
通讯作者：
Kuriyama, T
中科院分区：
文献类型：
--
作者：
Amano, S;Tatsumi, K;Kuriyama, T
目的：在肺动脉高压患者的肺血管中观察到前列环素合酶（PGIS）表达降低，并且前列环素（PGI（2））的生物合成可能在慢性血栓栓塞性肺动脉高压（CTEPH）中受损。它是由基因决定还是随着疾病的进展而发展尚不清楚。在PGIS基因的5 '上游启动子区检测到可变数目串联重复序列（VNTR）多态性。已经证明，等位基因的大小从9个碱基对的3个重复到7个重复不等，并且转录活性随着重复数目的增加而增加。本研究的目的是阐明PGIS基因的VNTR多态性和CTEPH在日本subjects.Methodology之间的关联：90例CTEPH患者和144名对照组进行了调查的VNTR多态性的存在。结果：前列环素合成酶基因VNTR多态性分为L等位基因（5、6、7个重复）和S等位基因（3、4个重复），其中L等位基因的频率为100 ~ 1000 Hz，S等位基因的频率为100 ~ 1000 Hz，S等位基因的频率为100 ~ 1000 Hz。CTEPH患者和对照组的等位基因和基因型的总体分布没有显着差异。LL基因型的患者有较高的血浆浓度的6-酮-前列腺素F-1 α比患者的LS和SS genotype.Conclusions：我们的研究结果表明，特定的VNTR多态性在5 '上游启动子区的PGIS基因调节前列环素的生产，但似乎没有与发展CTEPH在这个患者群体。
Objective: Decreased expression of prostacyclin synthase (PGIS) is observed in the lung vasculature of patients with pulmonary arterial hypertension and the biosynthesis of prostacyclin (PGI(2)) 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.Methodology: 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 A(2) 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 F-1alpha 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.