Association of the Caveolin Gene with Insulin Resistance and Hypertension

描述（由申请人提供）：本提案的长期目标是使用基因组技术来个性化异质性疾病高血压的预防和治疗策略，从而降低通常由这种疾病导致的发病率和死亡率。具体而言，该建议旨在确定高血压同质子集（中间表型）的基因组标记;高血压中的胰岛素抵抗。这一目标与国家护理研究所的目标是一致的，以确定易感基因的风险个体的干预措施，以中度风险的设计。本提案的具体目的是确定小窝蛋白基因（Cav-1）的多态性是否与非调节性高血压（高血压的中间表型）的胰岛素抵抗相关。这一目标将分三步进行分析。首先，将确定具有高血压同质子集（中间表型）的参与者，通过去除分析异质性遗传疾病的研究中经常存在的许多混杂变量，确保明确定义的研究人群。其次，将分析候选基因Cav-1，以确定该基因的多态性变化是否与高血压的特定同质子集相关。选择该候选基因是因为其作用机制和参与胰岛素信号传导和血管功能。第三，将使用正常血糖胰岛素钳夹测量胰岛素抵抗，以确定被鉴定为具有高血压同质子集和Cav-1基因多态性变体的参与者是否具有胰岛素抵抗。将比较两组相同大小的患者（非调节性高血压与低肾素高血压），以确定两组之间Cav-1多态性频率和胰岛素抵抗是否存在显著差异。相关性分析将确定Cav-1多态性与高血压胰岛素抵抗之间是否存在关联。这项拟议研究的结果将促进我们对胰岛素抵抗和高血压的遗传基础的理解，可能改变目前治疗慢性疾病的方法。具体而言，与胰岛素抵抗和高血压相关的遗传信息将促进未来的研究，以开发和实施护士主导的、患者特异性的而不是目前的非特异性干预措施，用于预防和治疗慢性疾病高血压。这些研究结果可直接影响公众健康，减低高血压引致的发病率和死亡率。具体而言，通过制定个性化的治疗方案，可能会实现更好的依从性。

DESCRIPTION (provided by applicant): 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.