Association of the Caveolin Gene with Insulin Resistance and Hypertension

描述(申请人提供)：这项建议的长期目标是使用基因组技术来个体化预防和治疗异质性高血压的策略，从而降低这种疾病经常导致的发病率和死亡率。具体地说，这项建议试图确定高血压的同质亚型(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一致，即确定高危个体的易感基因，以设计适度风险的干预措施。这项建议的具体目的是确定小窝基因(Cav-1)的多态是否与非调节性高血压(高血压的一种中间表型)的胰岛素抵抗有关。这一目标将分三步进行分析。首先，将确定具有相同高血压亚型(中间表型)的参与者，通过消除分析异质性遗传疾病的研究中经常存在的许多混淆变量，确保研究人群的明确定义。其次，将对候选基因Cav-1进行分析，以确定该基因的多态变化是否与高血压的特定同质性子集有关。选择这个候选基因是因为它的作用机制以及与胰岛素信号和血管功能的关系。第三，将使用正常血糖的胰岛素钳夹来测量胰岛素抵抗，以确定被确认患有高血压同质性亚组和Cav-1基因多态变种的参与者是否存在胰岛素抵抗。两组同等大小(非调节性高血压和低肾素高血压)将进行比较，以确定两组之间在Cav-1多态频率和胰岛素抵抗方面是否存在显著差异。相关分析将确定Cav-1基因多态性与高血压患者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，潜在地改变目前治疗慢性疾病的方法，具体地说，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、患者特定的干预措施，而不是目前的非特异性干预措施来预防和治疗慢性病高血压。这些研究结果可以降低高血压的发病率和死亡率，从而直接影响公众健康。具体地说，通过开发个性化治疗计划，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.