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
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