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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。原发性高血压是心血管疾病的主要危险因素，心血管疾病是美国的主要死亡原因。超过5000万美国人受到原发性高血压的影响，但其机制尚未确定。环氧合酶途径的血管活性花生四烯酸代谢物，即花生四烯酸，已被用于高血压的动物和人体研究。环氧化物11-12表二十碳三烯酸，推定的内皮衍生超极化因子（EDHF），由细胞色素P450 CYP 2C 9形成。CYP 2C 9基因多态性和慢代谢表型的高患病率，这可能会导致高血压患者的环氧化物水平的改变和EDRH的形成减少。CYP 2C 9基因多态性引起的血管活性环氧化物谱改变可能在原发性高血压中起机制作用。我们建议调查原发性高血压患者与健康受试者相比，CYP 2C 9多态性和血浆及尿类花生酸水平的患病率，以确定其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.