EFFECT OF GENETIC POLYMORPHISMS IN THE EPOXYGENASE PATHWAY ON SALT EXCRETION

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来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。已知细胞色素P450途径产生的花生四烯酸代谢产物环氧二十碳三烯酸（E3）在动物模型中抑制肾钠再吸收，并可能在盐敏感性和/或盐抵抗性高血压中可能受到干扰的健康人类受试者中具有相似的作用。P450途径（环氧酶途径）的遗传多态性可能导致E2、DHETS和肾盐排泄水平的改变，并可能在盐敏感性高血压中发挥机制性作用。 具体目标1：对高血压受试者进行环氧酶途径（CYP 2 J2、CYP 2C 8、CYP 2C 9和sEH）多态性的基因分型，并比较非裔美国人和高加索人人群中年龄和种族匹配对照的变异等位基因频率。 具体目标二：在非裔美国人和高加索人群中，确定盐负荷和盐消耗对盐敏感性（SS）和盐抵抗性（SR）高血压患者的尿和血浆花生四烯酸代谢产物的影响。 具体目标3：确定环氧合酶基因型对盐负荷和盐消耗反应的影响，并将这些影响与SS和SR高血压各个亚组的血浆和尿液花生四烯酸代谢物相关。

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. Arachidonic acid metabolities generated by the cytochrome P450 pathway, epoxyeicosatrienoic acid (EETs) are known to inhibit renal sodium reaborption in animal models and may have similar effects in healthy human subjects which may be perturbed in salt-sensitive and/or salt-resistent hypertension. Genetic polymorphisms in this P450 Pathway (the epoxygenase pathway) may lead to altered levels of EETs, DHETS and renal salt excretion and may play a mechanistic role in salt-sensitive hypertension. Specific Aim 1: Genotype hypertensive subjects for polymorphisms of the epoxygenase pathway (CYP2J2, CYP2C8, CYP2C9, and sEH) and compare the frequency of variant alleles age and race matched controls in African-American and Caucasian populations. Specific Aim 2: Determine the effect of salt loading and salt depletion on urinary and plasma arachidonic acid metabolites in salt-sensitive (SS) and salt-resistant (SR) hypertension in African-American and Caucasian populations. Specific Aim 3: Determine the effect of epoxygenase genotype on response to salt loading and salt depletion and correlate these effects with plasma and urinary arachidonic acid metabolites in various subgroups in SS and SR hypertension.