GENETIC EXPRESSION OF RISK GENES IN HYPERTENSION

描述（来自申请的逐字）：高血压是一种主要的 心血管疾病是美国女性死亡的主要原因。 大多数高血压研究都集中在男性身上。女性发病率较低 高血压的发病率一直持续到50岁， 女人的力量比男人大。因为50岁是 在美国女性更年期，这一观察表明，卵巢类固醇，目前 在绝经前状态，掩盖高血压的遗传易感性， 在绝经期失去这些类固醇， 高血压变得明显。我们已经证明，一个特定的中间体 原发性高血压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 高血压这种表型在绝经前妇女中并不常见， 年龄匹配的男性，但这种表型的频率在绝经期增加 男女平等。埃因霍温对许多 基因的RAAS，因此是一个主要的候选人，用于调节 基因型的表达和表型的改变 绝经前与绝经后妇女的频率。这一总体目标 建议是：（1）显示特定频率的差异 绝经前高血压妇女RAAS基因多态性的研究 比较绝经后高血压女性和男性，2）检验假设 对绝经后高血压妇女服用雌二醇 RAAS基因中的这些特异性多态性将改变 检测组织RAAS活性 根据这三个群体的特定基因型。

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.