Female gender & expression of risk genes in hypertension

性别 女性

• 批准号: 7010658
• 负责人: Ellen W Seely
• 金额: $ 22.7万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010658
• 关键词: adipocytes; age difference; aldosterone; angiotensinogen; cardiovascular disorder epidemiology; disease /disorder classification; disease /disorder etiology; estradiol; female; gender difference; gene environment interaction; gene expression; gene frequency; genetic polymorphism; genetic susceptibility; hormone therapy; human subject; human therapy evaluation; hypertension; menopause; patient oriented research; renin angiotensin system; women' s health

DESCRIPTION: (Adapted from the applicant's abstract) 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. Earlier studies by these workers have shown that a specific intermediate phenotype of essential hypertension is associated with polymorphism 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 Caucasian women compared to age-matched men but the frequency of this phenotype increased 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 polymorphism 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 estrasiol to postmenopausal hypertensive women with these specific polymorphism in RAAS genes will alter the intermediate phenotype and lower blood pressure, and 3) examine activity of the tissue RAAS according to specific genotypes in these three groups.

产品说明：（改编自申请人摘要）高血压是心血管疾病的主要原因，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。妇女在50岁之前的高血压发病率较低，50岁以后，妇女的高血压发病率高于男子。 由于50岁是美国妇女绝经的平均年龄，这一观察结果表明，卵巢类固醇，目前在绝经前的状态，掩盖遗传易感性高血压，并在绝经期这些类固醇的损失，遗传易感性高血压变得明显。 这些工作者的早期研究已经表明，原发性高血压的特定中间表型与血管紧张素原基因的多态性相关，其导致作为高血压的可能原因的肾素-血管紧张素-醛固酮系统（RAAS）的更大的组织活性。 与年龄匹配的男性相比，这种表型在绝经前白人女性中并不常见，但这种表型的频率在绝经后增加，男性和女性中变得相等。 雌激素对RAAS的许多基因有重要影响，因此是调节基因型表达的主要候选者，并负责绝经前与绝经后妇女表型频率的变化。 本提案的总体目标是：1）证明与绝经后高血压妇女和男性相比，绝经前高血压妇女中RAAS基因的特异性多态性频率的差异，2）检验对具有RAAS基因中这些特异性多态性的绝经后高血压妇女施用雌激素将改变中间表型和降低血压的假设，（3）检测三组中不同基因型的组织RAAS活性。