GENETICS OF HOSTILITY & GLUCOSE METABOLISM

敌意的遗传

• 批准号: 6831883
• 负责人: RICHARD SAMUEL SURWIT
• 金额: $ 20.64万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831883
• 关键词: African American; angers; behavioral /social science research tag; behavioral genetics; behavioral medicine; cardiovascular disorder risk; caucasian American; clinical research; gender difference; gene environment interaction; gene expression; genetic polymorphism; genetic susceptibility; glucose metabolism; human subject; insulin sensitivity /resistance; linkage disequilibriums; serotonin

Studies from this project have shown that hostility is related to various measures of glucose metabolism. Furthermore, hostility is differentially related to glucose metabolism in Caucasian and African American male and female subjects. While high hostile Caucasian subjects are relatively hyperinsulinemic and insulin resistant compared to low hostile Caucasian subjects, high hostile African Americans have higher fasting glucose levels than low hostile African Americans. Furthermore, the effects of hostility on insulin resistance are more pronounced in females. We have also shown that polymorphisms of two genes that are critically involved in regulation of serotonergic function throughout the body are associated with increased fasting glucose and insulin in subjects with high 5HIAA in cerebral spinal fluid. To further explore these findings, this project will assess measures of glucose metabolism (fasting glucose and insulin, glucose tolerance, HbA1C, and insulin sensitivity) as well as other variables related to the metabolic syndrome (lipids, BMI, central adiposity and blood pressure) in a sample comprised of a minimum of 400 probands (half African American and half Caucasian, half men and half women, and half scoring in the top and half in the bottom 20% on a valid, measure of hostility that predicts CVD and has heritability estimates of 40-55%) and at least one sibling for every proband, to make a total sample of 800-1200 subjects who will participate in the protocol of this project. Our first goal will be to evaluate a minimum of 4 l candidate genes/loci that act either directly or in interaction with environmental factors, or as a function of linkage disequilibrium with other sites or membership in haplotypes, to influence expression of hostility and the individual components of the metabolic syndrome as well as their tendency to cluster. Furthermore, in collaboration with Projects 1 and 3, we will identify candidate genes/loci that account for the clustering of these metabolic abnormalities with cardiovascular, neuroendocrine, platelet function and inflammatory markers assessed in those Projects. Such knowledge could increase understanding of the contribution of gene-environment interactions to pathogenic mechanisms whereby psychosocial and biobehavioral risk factors increase CVD risk, thereby helping to identify highly susceptible persons who might be targets for primary prevention trials.

该项目的研究表明，敌意与葡萄糖代谢的各种措施有关。此外，敌对情绪与高加索和非裔美国人和女性受试者的葡萄糖代谢有不同的关系。尽管与低敌对的高加索受试者相比，高敌对的高加索受试者相对高胰岛素和胰岛素具有抗药性，但高敌对的非裔美国人的禁食葡萄糖水平高于低敌对的非洲裔美国人。此外，敌对性对胰岛素抵抗的影响在女性中更为明显。我们还表明，在整个人体中严格涉及血清素能功能的两个基因的多态性与大脑脊髓液中高5HIAA受试者的空腹葡萄糖和胰岛素增加有关。为了进一步探索这些发现，该项目将评估葡萄糖代谢的度量（禁食葡萄糖和胰岛素， 在一个样本中，与代谢综合征（脂质，BMI，中央肥胖和血压）相关的其他变量以及至少400个概率（一半的非洲人和一半的男性，一半的男性和一半的衡量标准均可在400个概率中，有效的效果，葡萄糖耐量，HBA1C和胰岛素敏感性）以及与代谢综合征（脂质，BMI，中央肥胖和血压）相关的其他变量预测了一半的效果。遗传力估计为40-55％），至少一个兄弟姐妹 每一个证据，都是将参与该项目协议的800-1200名受试者的总样本。我们的第一个目标是评估直接起作用或与环境因素相互作用的至少4 L候选基因/基因座，或者是与其他站点不平衡的函数，与其他站点或单倍型中的成员不平衡，以影响敌对性的表达和代谢综合征的各个成分以及它们的趋势 簇。此外，在与项目1和3的合作中，我们将确定候选基因/基因座，这些基因/基因座可以用这些项目中评估的心血管，神经内分泌，血小板功能和炎症标记来解释这些代谢异常。这样的知识可以增加对基因环境贡献的理解 与致病机制的相互作用，从而使心理和生物行为风险因素增加了CVD风险，从而有助于识别可能是初级预防试验目标的高度敏感人。