The ultimate goal of the entire SCOR is to identify genes which influence blood pressure and thus are responsible for the development of hypertension. In order to achieve this goal, the aim of Project 1 is to identify and intensively phenotype families which have been ascertained via an index case with hypertension. Because of the growing evidence for the importance of insulin resistance in hypertension, as well as the high prevalence of insulin resistance in the Mexican American population, our study places great emphasis on examination of insulin resistance as an intermediate phenotype in this ethnic group. Through careful and intensive physiologic evaluation, insulin resistance and other intermediate phenotypes integral to blood pressure regulation will be identified. Importantly, the interrelationships among these phenotypes will be examined, resulting in a better understanding of the physiologic processes which result in altered blood pressure and, by investigation of the familiality of these processes, a better understanding of the genetics of hypertension as well. We hope to determine how insulin resistance interacts with other important physiologic mechanisms, particularly salt sensitivity, in affecting blood pressure by examining the relationships of these phenotypes in individuals at high risk for hypertension (i.e. the young adult offspring of affected individuals), as well as by examining familial clustering of insulin resistance with specific combinations of other intermediate phenotypes. The detailed physiologic data collected in this project will be invaluable for both the systematic mapping and candidate gene quantitative sibpair analyses that will be performed in Project 2. The extensive phenotyping of 800- 1000 individuals from 200 Mexican American families with hypertension which will be accomplished by this project will provide a truly unique resource for the investigation of the genetic basis of hypertension in Mexican Americans. The studies performed up to now have relied upon either large numbers of individuals who have undergone only limited evaluation or upon intensive investigation of relatively small numbers of individuals from a limited number of families. This in-depth investigation of a large number of families will afford much greater power in finding the genes for hypertension and makes us confidant that our goals will be achieved.
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