THE EFFECT OF CYTOCHROME P450 CYP2C9 GENOTYPE AND PHENOTYPE ON EICOSANOID METAB

细胞色素P450 CYP2C9基因型和表型对二十烷酸代谢的影响

• 批准号: 7376239
• 负责人: ALBERT W DREISBACH
• 金额: $ 0.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376239
• 关键词: EFFECT; CYTOCHROME; P450; CYP2C9; GENOTYPE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Essential hypertension is a major risk factor for cardiovascular disease which is the leading cause of death in the United States. Over 50 million Americans are effected by essential hypertension but its mechanisms have not yet been defined. Vasoactive arachidonic acid metabolites of the epoxygenase pathway, the expoxides, have been implicated in animal and human studies of hypertension. The epoxide 11-12 epieicosatrienoic acid, the putative endothelium derived hyperpolarizing factor (EDHF), is formed by cytochrome P450 CYP2C9. CYP2C9 exhibits a high prevalence of genetic polymorphisms and slow metabolizer phenotype which may lead to altered levels of epoxides and reduced formation of EDRH in hypertensive patients. The altered vasoactive epoxide profile produced by CYP2C9 genetic polymorphisms may play a mechanistic role in essential hypertension. We propose to investigate the prevalence of CYP2C9 polymorphisms and plasma and urinary eicosanoid levels in patients with essential hypertension compared to healthy subjects to define their role in essential hypertension.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。原发性高血压是心血管疾病的主要危险因素，而心血管疾病是美国的主要死亡原因。超过 5000 万美国人患有原发性高血压，但其机制尚未明确。环氧化酶途径的血管活性花生四烯酸代谢物，即环氧化物，与动物和人类高血压研究有关。环氧化物 11-12 表二十碳三烯酸，即假定的内皮衍生超极化因子 (EDHF)，由细胞色素 P450 CYP2C9 形成。 CYP2C9 表现出高患病率的遗传多态性和慢代谢表型，这可能导致高血压患者环氧化物水平改变并减少 EDRH 形成。 CYP2C9 基因多态性产生的血管活性环氧化物谱的改变可能在原发性高血压中发挥机制作用。我们建议调查原发性高血压患者与健康受试者相比 CYP2C9 多态性的患病率以及血浆和尿类二十烷酸水平，以确定其在原发性高血压中的作用。