The long term objective of this proposal is to use genomic technology to individualize prevention and treatment strategies for the heterogeneous disorder hypertension thereby, decreasing the morbidity and mortality that often results from this condition. Specifically, this proposal seeks to identify genomic markers for a homogeneous subset (intermediate phenotype) of hypertension;insulin resistance in hypertension. This objective is consistent with the National Institute of Nursing Research's goal to identify susceptibility genes for at-risk individuals for the design of interventions to moderate risk.
The specific aim of this proposal is to determine if polymorphisms in the caveolin gene (Cav-1) are associated with insulin resistance in nonmodulating hypertension (an intermediate phenotype of hypertension).
This aim will be analyzed in a three step process. First, participants with homogeneous subsets of hypertension (intermediate phenotypes) will be identified, ensuring a well-defined study population by removing the many confounding variables often present in studies analyzing heterogeneous genetic disorders. Second, a candidate gene, Cav-1, will be analyzed to determine whether polymorphic changes in the gene are associated with a specific homogeneous subset of hypertension. This candidate gene was chosen secondary to its mechanism of action and involvement with insulin signaling and vascular function. Third, insulin resistance will be measured using a euglycemic insulin clamp to determine if participants identified as having the homogeneous subset of hypertension and polymorphic variants of the Cav-1 gene are insulin resistant. Two groups of equal size (non-modulating hypertension versus low-renin hypertension) will be compared to determine whether a significant difference exists between the two groups for both Cav-1 polymorphism frequencies and insulin resistance. A correlation analysis will determine whether an association exists between Cav-1 polymorphisms and insulin resistance in hypertension. The results of this proposed study will advance our understanding of the genetic underpinnings of insulin resistance and hypertension, potentially altering current approaches to chronic illnesses, Specifically, genetic information related to insulin resistance and hypertension will foster future research to develop and implement nurse led, patient specific rather than the current non-specific interventions for the prevention and treatment of the chronic illness hypertension. These study findings could directly affect public health by reducing the morbidity and mortality resulting from hypertension. Specifically, through the development of individualized treatment programs, better compliance will likely be achieved.
