大规模人群中原发性高血压发病机制中盐敏感性和交感神经调节的遗传作用(研究方案及预试验)

Role of Genetic Mechanism of Salt Sensitivity and Sympathetic Activity in the Pathogenesis of EH in Population(Protocol and Pilot Study)

目的 探讨在中国汉族人群中 ,盐敏感及交感神经调节的影响在原发性高血压发病机制中的作用。方法学 在选定的现场调查中心对该地区所登记的家庭进行随机抽样 ,同时在指定的高血压门诊筛选病人 ,最终共入选 2 0 0个家庭、约 10 0 0位受试者。采用连锁分析方法对入选家庭中年龄为 18～ 5 9岁的核心成员肾素系统的遗传变异与血压及高血压之间的关系进行研究。采用严格标准化的流行病学调查方法、严格的质量控制来确定血压与其他特征相结合的综合表型。常规血压为 2次独立家访测量的血压 (共 10个读数 )的平均值。确定综合表型的方法包括 2 4小时动态血压监测 ,作为心血管系统自主调节指数的心率变异性能谱分析及作为钠敏感性的内源性锂清除率测定。问卷将调查个人及家庭的医疗史及重要的生活方式。除血常规检查 ,还将测定血生化及血浆肾素活性、血管紧张素原浓度及血管紧张素转换酶的活性及 2 4小时尿电解质排泄量。预期结果 在中国 ,高血压的标化患病率为 11.2 6 % [2 ] ,其主要并发症为脑卒中 ,而后者是致残的主要危险。本研究将促进我国心血管疾病遗传学的研究 ,将有助于高血压及其并发症的预防及治疗 ,对我国公共卫生事业具有重要意义。预试验结果 共调查 4 8例 (男 2 0 ,女 2 8) ,平均年龄 38.

Aim To explore the role of genetic mechanism of salt sensitivity and sympathetic activity in the pathogenesis of essential hypertension in populations in China. Methodology Via random population sampling and enrollment at specialized hypertension clinics, 200 families (nearly 1000 subjects) will be recruited. In subjects aged 18～59 years, the relationship between blood pressure(BP), HT and genetic variation in the renin system will be investigated using linkage analysis. Strictly standardized epidemiological methods and rigorous quality control will be used to determine complex phenotypes consisting of BP and combination with other traits. Modern methods to define complex phenotypes include 24-hour ambulatory BP monitoring, power spectral analysis of heart rate variability as index of the autonomic nervous modulation of the cardiovascular system, and measurement of the endogenous lithium clearance as index of salt sensitivity. A questionnaire will inquire into personal and familial medical history and important life style factors. In addition to usual measurement,blood biochemistry will included plasma renin activity, angiotensinogen concentration and angiotensin converting enzyme activity examined also. The electrolyte and aldosterone excretion will be measured in 24 hours urine samples. Expected outcomes The prevalence of HT in China is 11.26% and the main complication is stroke which is the main cause of incapacitated. This project will lead to the more rational prevention and treatment of HT and its incapacitating complications and will help to curb the epidemic of cardiovascular disease in China. It will promote genetic and cardiovascular research in China and define new goals and markets for the pharmaceutical industry. Pilot Study Results Total 48 cases(male 20,Female 28),average 38.6±12.3 years old were investigated. The sitting average SBP was 123.3±18.2 mmHg,DBP 78.3±7.9 mmHg, and heart rate 79 beat/min. According Chinese Hypertension Guideline there are 11 subjects(22.9%,7 male and 4 female) were defined as hypertension. The average body mass index(BMI) was 24.1±3.2(18.4～31.9),the waist/hip ratio were 0 81±0 08(0 60～1.04). The plasma glucose ,electrolytes(Na,K,Cl),HDL c,LDL c,CT,and TG were within normal range. Plasma renin activity 3.38±1.84 ng·ml -1 ·h -1 and angiotensin concentration 0 23±0 06 μmol/L.