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.

描述：（改编自申请人的摘要）高血压是心血管疾病的主要原因，而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。女性高血压发病率较低，50岁之前，女性高血压发病率高于男性。 由于美国女性绝经的平均年龄是 50 岁，这一观察结果表明，绝经前状态下存在的卵巢类固醇掩盖了高血压的遗传倾向，而随着绝经期这些类固醇的丧失，高血压的遗传倾向变得明显。 这些工作人员的早期研究表明，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，血管紧张素原基因的多态性导致肾素-血管紧张素-醛固酮系统（RAAS）的组织活性增强，可能是高血压的原因。 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，在男性和女性中变得相等。 雌二醇对 RAAS 的许多基因具有重要影响，因此是调节基因型表达并负责绝经前与绝经后女性表型频率变化的主要候选者。 该提案的总体目标是：1) 证明绝经前高血压女性与绝经后高血压女性和男性相比，RAAS 基因特定多态性频率存在差异，2) 检验雌二醇治疗绝经后高血压的假设RAAS 基因中具有这些特定多态性的女性将改变中间表型并降低血压，并且 3) 检查组织的活性RAAS 根据这三组的具体基因型。