C242T POLYMORPHISM OF P22PHOX GENE DOES NOT DECREASE RISK OF CAD

P22PHOX 基因的 C242T 多态性不会降低 CAD 风险

• 批准号: 6109302
• 负责人: A A QUYYUMI
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6109302
• 关键词: Japanese; angiography; atherosclerosis; blood flow measurement; clinical research; coronary disorder; gene frequency; genetic polymorphism; genetic susceptibility; human subject; racial /ethnic difference; single strand conformation polymorphism; vascular endothelium

Patients with coronary artery disease (CAD) have impaired endothelium-dependent vasodilation due in part to an increase in superoxide anion levels. p22phox, an essential component of the NADPH oxidase, is thought to play a critical role in the generation of superoxide anions in the vessel wall. The C242T polymorphism, located in the potential heme-binding site of the p22phox gene, has recently been reported to confer a protective effect on CAD risk in a Japanese study population. By using a single-stranded conformation polymorphism analysis, we first investigated the allelic frequency of the C242T polymorphism in the U.S. population. In a population of 176 patients with no known history of heart disease (control), the prevalence of the allele (heterozygous + homozygous) was 59.7%, which was significantly higher than previously reported in the Japanese population. We next analyzed 246 patients (82% Caucasian) undergoing angiography for diagnosis of CAD. In 149 patients with any angiographic evidence of atherosclerosis, the prevalence of the C242T polymorphism was 64.4%, whereas in 97 patients with angiographically smooth coronary arteries, the prevalence was 55.6% (Chi-square=N.S.). We next investigated the effect of the polymorphism upon microvascular endothelial function in a subset of 140 patients undergoing angiography using intracoronary acetylcholine (ACH) (3-100 mcg/min). As measured using Doppler flow wire, vasodilation in response to ACH was similar in patients with and without the C242T allele. Thus, the prevalence of the C242T polymorphism, which is higher in the U.S. than in the Japanese population, does not confer protection from endothelial dysfunction of CAD.

冠心病(CAD)患者有 血管内皮依赖性舒张功能受损的部分原因是 超氧阴离子水平升高。P22Phox，一种必不可少的 NADPH氧化酶的组成部分，被认为起着关键作用 在血管壁上产生超氧阴离子。这个 C242T多态，位于中国人的潜在血红素结合部位 P22Phox基因，最近被报道赋予保护性的 在日本研究人群中对冠心病风险的影响。通过使用 单链构象多态性分析，我们首先 调查C242T多态在中国汉族人群中的等位基因频率 美国人口。在176名未知疾病患者中 心脏病史(对照)、等位基因的患病率 (杂合子+纯合子)为59.7%，差异有统计学意义 这一比例高于此前报道的日本人口。我们是下一个 对246例(82%)接受血管造影的患者进行了分析 冠心病的诊断。在149名有血管造影证据的患者中 在动脉粥样硬化中，C242T多态的患病率为 64.4%，而在97例血管造影顺利的患者中 冠状动脉，患病率为55.6%(卡方=N.S.)。 接下来，我们研究了这种多态对 140例患者的微血管内皮细胞功能 冠状动脉内应用乙酰胆碱(ACH)行血管造影术 (3-100微克/分钟)。如使用多普勒血流线测量的， 急性脑出血患者的血管扩张反应相似。 没有C242T等位基因。因此，C242T的流行 多态，在美国比在日本更高 人群，不提供针对内皮功能障碍的保护 计算机辅助设计。