SODIUM TRANSPORT: GENETICS & HYPERTENSION

钠转运：遗传学

• 批准号: 3341442
• 负责人: STEPHEN T TURNER
• 金额: $ 40.13万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341442
• 关键词: adolescence (12-20); alleles; cardiovascular disorder diagnosis; cardiovascular disorder epidemiology; cardiovascular disorder prevention; case history; disease /disorder model; disease /disorder proneness /risk; erythrocyte membrane; familial hypertension; gene expression; genotype; human subject; mathematical model; membrane permeability; middle childhood (6-11)

The overall objective of this research project is to determine whether genetic alterations in pathways of sodium ion (Na) transport in the red blood cvells (RBC) of children can predict their risk of developing primary hypertension (PH) in adulthood. The proposed investigation focuses on one characteristic of in vitro Na transport in the human RBC-maximal rate of sodium-lithium counter-transport (Na-Li CNT). This trait will first be measured in a random sample of 1,500 school children between 7 and 18 years of age in Rochester, Minnesota, to characterize the distribution in the population at large. The utility of increased Na-Li CNT as a predictor of elevated blood pressure (BP) in the young will be determined and compared with other predictive markers (e.g., age, weight, sex). Next, approximately 300 children will be randomly selected as index cases for familiy studies which will assess the contribution of genetic factors to the inter-individual variability of Na-Li CNT in the population. Complex segregation analysis of pedigree data will be carried out to determine the most likely mode for genetic transmission of the Na-Li CNT phenotype. Specifically, the hypothesis that there is a single gene locus segregating for two alleles having a major effect on Na-Li CNT will be tested. Finally, the baseline genetic information about Na-Li will be related to the prevalence of primary hypertension in the families of index children. The multiple logistic regression model will be used to ask whether Na-Li CNT levels in index children and for aggregation of Na-Li CNT levels in their first-degree relatives can predict prevalence of primary hypertension in the adult members of the family. Information regarding Na-Li CNT and blood pressure obtained from these studies will be applicable to the white population of the United States in general. This research will help elucidate the genetic basis of alterations in membrane Na transport in the human RBC and may lead to simple methods to help identify children at increased risk of developing primary hypertension in adulthood

这项研究项目的总体目标是确定 红壤中钠离子(Na)运输途径的遗传变化 儿童的血细胞(RBC)可以预测他们患原发性心脏病的风险 成年期高血压(PH)。拟议中的调查集中在一个 人红细胞体外钠转运特性--最大钠转运速率 钠锂反转运(Na-Li CNT)。这一特点首先将是 在随机抽样的1,500名7至18岁学龄儿童中进行测量 明尼苏达州罗切斯特的年龄分布特征 广大的人口。钠锂碳纳米管升高作为糖尿病预测指标的价值 年轻人的高血压(BP)将被测定并比较 与其他预测性指标(例如，年龄、体重、性别)相关联。下一首, 大约300名儿童将被随机选为 家庭研究将评估遗传因素对 钠锂碳纳米管在种群中的个体间变异性。复合体 将对系谱数据进行分离分析，以确定 Na-Li CNT表型最有可能的遗传传播方式。 具体地说，存在单个基因座分离的假设 对于对钠锂碳纳米管有重大影响的两个等位基因，将进行检测。 最后，关于纳力的基线遗传信息将与 指标儿童家庭的高血压患病率。 多元Logistic回归模型将被用来询问纳丽是否 指数儿童的CNT水平和儿童Na-Li CNT水平的聚集 他们的一级亲属可以预测原发性高血压的患病率 在这个家庭的成年成员中。关于钠锂碳纳米管的信息和 从这些研究中获得的血压将适用于白人 美国总人口的总和。这项研究将会有所帮助 细胞膜钠转运改变的遗传学基础 人类红细胞，并可能导致简单的方法来帮助识别儿童在 成年后发展为原发性高血压的风险增加