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

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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.