Genetics of Hypertension

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DESCRIPTION (provided by applicant): Hypertension is the most common chronic medical condition worldwide and in the US alone 72 million people are affected with the condition. Of these, 90% developed hypertension for no known reasons, also called as Essential hypertension. Although it is well known that genetics play a major role in conferring susceptibility to develop essential hypertension, the identities of the genes/genetic factors that are causally responsible for essential hypertension remain largely unknown. This is the single biggest rate-limiting factor in advancing our understanding of the etiology of essential hypertension. Using a rat genetic model for hypertension, we have located a 793.5 kb region on the rat genome as responsible for controlling BP. This region in rats and the orthologous regions in humans, contains two genes, only one of which contains significant variations. Analysis of single nucleotide polymorphisms in humans indicates that select variants of this gene are also associated with human essential hypertension. This observation defines the need to further investigate the function of this novel gene, which constitutes one of the specific aims of our proposal. The other aims are to further genetically dissect the critical 793.5kb region to obtain further evidence for the candidacy of this prioritized candidate gene and/or other QTL effectors by trapping the BP effect within the shortest possible rat genomic segment and to construct a transgenic-congenic strain to test the QTL effect. The significance of our proposal is that it is potentially on the verge of unraveling a novel genetic factor in the etiology of Essential Hypertension. PUBLIC HEALTH RELEVANCE: Genetics is well recognized to be an important factor that contributes to the development of hypertension, which leads to cardiovascular related illnesses. The research work described in this proposal pertains to improve our current, significantly limited understanding of the identities of genes that control blood pressure. Knowledge gained through successful completion of the work described is expected to pin-point at least one genetic factor that has not been previously suspected to cause hypertension.