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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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死亡的主要原因。超过5000万美国人患有原发性高血压，但其发病机制尚未明确。环氧合酶途径的血管活性花生四烯酸代谢物，即环氧化物，在高血压的动物和人类研究中都有涉及。环氧化合物11-12表二碳三烯酸，被认为是内皮衍生的超极化因子（EDHF），由细胞色素P450 CYP2C9形成。CYP2C9表现出较高的遗传多态性和缓慢的代谢表型，这可能导致高血压患者环氧化物水平改变和EDRH形成减少。CYP2C9基因多态性引起的血管活性环氧化物谱的改变可能在原发性高血压中起机制作用。我们建议研究原发性高血压患者中CYP2C9多态性的患病率以及血浆和尿液类二十烷酸水平，并与健康受试者进行比较，以确定它们在原发性高血压中的作用。

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.