RED CELL SODIUM TRANSPORT: GENETICS AND HYPERTENSION

红细胞钠转运：遗传学和高血压

• 批准号: 3341445
• 负责人: STEPHEN T TURNER
• 金额: $ 25.33万
• 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 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341445
• 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

本研究项目的总体目标是确定 红细胞中钠离子（Na）转运途径的遗传改变 儿童的红细胞（RBC）可以预测他们患原发性肝癌的风险。 成年期高血压（PH）。 调查重点是一个 人红细胞体外钠转运的特征-最大速率 钠-锂反向传输（Na-Li CNT）。 这一特点将首先是 对1,500名7至18岁的学童进行了随机抽样调查 年龄在罗切斯特，明尼苏达州，以表征分布在 一般人口。 增加的Na-Li CNT作为预测的效用 将测定和比较年轻人的血压升高（BP） 与其它预测标记（例如，年龄、体重、性别）。 接下来， 将随机选择约300名儿童作为索引病例， 家庭研究，将评估遗传因素的贡献， 群体中Na-Li CNT的个体间变异性。 复杂 将进行谱系数据的分离分析，以确定 Na-Li CNT表型的遗传传递的最可能模式。 具体地说，假设有一个单一的基因位点分离， 将测试对Na-Li CNT具有主要影响的两个等位基因。 最后，关于钠-锂的基线遗传信息将与 指数儿童家庭中原发性高血压的患病率。 多元逻辑回归模型将被用来询问钠-锂是否 指数儿童中的CNT水平和指数儿童中Na-Li CNT水平的汇总 其一级亲属可以预测原发性高血压的患病率 在家庭的成年成员中。 关于Na-Li CNT和 从这些研究中获得的血压将适用于白色 总的来说，美国的人口。 这项研究将帮助 阐明膜钠转运改变的遗传基础， 人类红细胞，并可能导致简单的方法，以帮助确定儿童在 成年后患原发性高血压的风险增加