GENETIC EXPRESSION OF RISK GENES IN HYPERTENSION

描述(来自申请表的逐字)：高血压是一种主要的 心血管疾病是美国女性的主要死亡原因。 大多数关于高血压的研究都集中在男性身上。女性的发病率较低 在50岁之前，高血压的发病率在 女人变得比男人更伟大。因为50岁是 在美国更年期妇女中，这一观察表明卵巢类固醇存在 在绝经前状态，掩盖高血压的遗传易感性和 随着更年期这些类固醇的丢失，遗传易感性 高血压变得很明显。我们已经证明了一种特定的中间体 高血压病患者的表型与基因多态性相关 血管紧张素原基因，导致更大的组织活性 肾素-血管紧张素-醛固酮系统(RAAS)可能是高血压的原因之一 高血压。这种表型在绝经前妇女中并不常见，相比于 年龄匹配的男性，但这种表型的频率在绝经后增加 变得男女平等。雌二醇对许多人有重大影响 RAAS的基因，因此是调节 基因表达与表型变化的关系 绝经前和绝经后妇女的频率。这个项目的总体目标是 建议的目的是：1)展示特定词汇使用频率的差异 绝经前高血压妇女AS患者RAAS基因多态性的研究 与绝经后的女性和男性相比，2)验证了这一假设 雌激素对绝经后高血压妇女的治疗 RAAS基因的这些特定的多态将改变中间产物 表型和降压，3)检测组织RAAS活性 根据三组中特定的基因分型。

DESCRIPTION (Verbatim from the application): Hypertension is a major contributor to cardiovascular disease, the leading cause of death in US women. Most studies of hypertension have focused on men. Women have a lower incidence of hypertension until age 50 at which time, the incidence of hypertension in women becomes greater than that in men. Since age 50 is the average age of menopause in US women, this observation suggests that ovarian steroids, present in the premenopausal state, mask genetic predisposition to hypertension and that with loss of these steroids at menopause, genetic predisposition to hypertension becomes manifest. We have shown that a specific intermediate phenotype of essential hypertension is associated with polymorphisms of the angiotensinogen gene which result in greater tissue activity of the renin-angiotensin-aldosterone system (RAAS) as a possible cause of hypertension. This phenotype is uncommon in premenopausal women compared to age-matched men but the frequency of this phenotype increases at menopause becoming equal in men and women. Estradiol has major effects on many of the genes of the RAAS and therefore is a prime candidate for modulating the expression of genotype and being responsible for the change in phenotype frequency in pre versus postmenopausal women. The overall objectives of this proposal are to: 1) demonstrate a difference in frequency of specific polymorphisms of genes of the RAAS in premenopausal hypertensive women as compare to hypertensive postmenopausal women and men, 2) test the hypothesis that the administration of estradiol to postmenopausal hypertensive women with these specific polymorphisms in RAAS genes will alter the intermediate phenotype and lower blood pressure, 3) examine activity of the tissue RAAS according to specific genotypes in these three groups.