Genetics and Personalized Medicine: From Population Studies to Clinical Therapy

遗传学和个性化医疗：从人口研究到临床治疗

• 批准号: 7936114
• 负责人: CHRISTIE Mitchell BALLANTYNE
• 金额: $ 50万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936114
• 关键词: Genetics; Personalized; Medicine; Population; Studies

DESCRIPTION (provided by applicant): We propose to expand the research focus of the Center for Cardiovascular Disease Prevention by hiring an independent faculty recruit trained in human genetics, who will have a joint appointment in the Departments of Medicine and Molecular and Human Genetics at Baylor College of Medicine, to perform research in two main areas that are directly relevant to improving prevention of coronary heart disease (CHD). He/she will establish effective tools for assessment and stratification of CHD risk based on genetic variation, mainly single nucleotide polymorphisms (SNPs). He/she will fully characterize known and novel genes and genomic regions that affect high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and CHD in a special subpopulation consisting of individuals in the upper and lower extremes for TG or HDL-C. The overall strategy of this approach has clear therapeutic goals: 1. Better accuracy of risk prediction and classification, based on the individual's genetic information, thus enabling more appropriate preventive treatment. 2. Identification of genes and genomic regions associated with HDL-C, TG, CHD risk, and response to commonly used drugs to treat lipid disorders. Achieving these goals will develop and extend inter- and intra-institutional collaborations that are already ongoing. Data from the largest prospective cohort studies in the United States-the Atherosclerosis Risk in Communities (ARIC), Candidate Gene Association Resource (CARE), and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) studies-will be analyzed by the recruit in close collaboration with the Department of Molecular and Human Genetics at Baylor College of Medicine and the Human Genetics Center at The University of Texas School of Public Health to identify SNPs associated with low HDL-C, high TG, and CHD risk. Genes found by the association studies will be sequenced by the Human Genome Sequencing Center at Baylor College of Medicine in a population of patients with low HDL-C and high TG participating in a double-blind study of statin and fibrate therapy, to examine the association of sequence variations in the genes with HDL-C and TG levels, and to determine the influence of these genes on lipid changes in response to commonly used drugs. Genetic information will therefore be applied in an effort to refine CHD risk assessment and to improve risk reduction through personalized preventive therapy. Cardiovascular disease remains the leading cause of death and medical expenses in the United States. Prevention of cardiovascular disease can be improved by using recent genetic discoveries to identify who is at risk of developing a heart attack and by improved understanding of the genes that control the levels of fats (triglycerides and HDL ["good"] cholesterol) in blood.

描述（由申请人提供）：我们建议通过聘请一名接受过人类遗传学培训的独立教师来扩大心血管疾病预防中心的研究重点，该教师将在贝勒医学院的医学系和分子与人类遗传学系担任联合职务，以在两个与改善冠心病（CHD）预防直接相关的主要领域进行研究。他/她将根据遗传变异，主要是单核苷酸多态性（SNP），建立有效的工具来评估和分层CHD风险。他/她将充分表征已知的和新的基因和基因组区域，影响高密度脂蛋白胆固醇（HDL-C），甘油三酯（TG）和CHD在一个特殊的亚群组成的个人在上限和下限的TG或HDL-C。这种方法的总体策略具有明确的治疗目标：1。根据个人的遗传信息，提高风险预测和分类的准确性，从而能够进行更适当的预防性治疗。2.与HDL-C、TG、CHD风险相关的基因和基因组区域的鉴定，以及对常用药物治疗血脂紊乱的反应。实现这些目标将发展和扩大目前正在进行的机构间和机构内合作。数据来自美国最大的前瞻性队列研究-社区动脉粥样硬化风险（ARIC），候选基因关联资源（CARE），基因组流行病学中的心脏和衰老研究队列（CHARGE）研究-将由招募人员与贝勒医学院分子和人类遗传学系以及德克萨斯大学人类遗传学中心密切合作进行分析。公共卫生部门鉴定与低HDL-C、高TG和CHD风险相关的SNP。相关性研究发现的基因将由贝勒医学院人类基因组测序中心在参与他汀类药物和贝特类药物治疗双盲研究的低HDL-C和高TG患者人群中进行测序，以检查基因序列变异与HDL-C和TG水平的相关性，并确定这些基因对常用药物引起的脂质变化的影响。因此，遗传信息将被应用于改善CHD风险评估，并通过个性化预防治疗来降低风险。 心血管疾病仍然是美国死亡和医疗费用的主要原因。通过利用最近的基因发现来识别谁有心脏病发作的风险，并通过更好地了解控制血液中脂肪（甘油三酯和高密度脂蛋白[“好”]胆固醇）水平的基因，可以改善心血管疾病的预防。