Genetic Analysis of HIV Complications

HIV并发症的基因分析

基本信息

批准号：
7624202
负责人：
ALEXANDRA MANGILI
金额：
$ 12.28万
依托单位：
TUFTS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7624202
关键词：
Adverse effects Advisory Committees Affect Anti-Retroviral Agents Apolipoprotein E Apolipoproteins Atazanavir Atherosclerosis Award Biometry Calcium Candidate Disease Gene Cardiovascular Diseases Cardiovascular system Characteristics Chronic Clinical Clinical Investigator Communicable Diseases Complex Coronary DNA Data Development Diagnosis Dietary Factors Dietary Intervention Dietary intake Disease Dyslipidemias Environment Environmental Risk Factor Epidemiologic Studies Event Fellowship Funding Future General Population Genes Genetic Genetic Determinism Genetic Polymorphism Genetic Variation Genetic screening method Genotype Goals Guidelines HIV HIV Infections HIV Seropositivity HIV-Associated Lipodystrophy Syndrome Highly Active Antiretroviral Therapy Incidence Indinavir Individual Infection Insulin Resistance Intervention K-Series Research Career Programs Knowledge Lead Learning Link Lipids Longitudinal Studies Lopinavir/Ritonavir Mentored Patient-Oriented Research Career Development Award Mentors Metabolic Metabolic syndrome Morbidity - disease rate Nutritional status Outcome Participant Patient Care Patients Pattern Peroxisome Proliferator-Activated Receptors Persons Pharmaceutical Preparations Pharmacogenetics Phenotype Plasma Play Population Predisposition Prevention strategy Principal Investigator Public Health Qualifying Recommendation Research Research Personnel Risk Risk Factors Ritonavir Role Sampling Stavudine Stratification Supervision Surrogate Markers Techniques Tenofovir Testing Thick Translating Treatment Protocols Variant adiponectin antiretroviral therapy apolipoprotein E-1 atherogenesis cardiovascular risk factor career career development clinical epidemiology cohort design genetic analysis genetic epidemiology genetic risk factor high risk innovation intima media lipoprotein lipase mortality novel nutrition patient oriented patient oriented research perilipin premature premature atherosclerosis prevent programs response skills tool treatment effect

Adverse effects Advisory Committees Affect Anti-Retroviral Agents Apolipoprotein E Apolipoproteins Atazanavir Atherosclerosis Award Biometry Calcium Candidate Disease Gene Cardiovascular Diseases Cardiovascular system Characteristics Chronic Clinical Clinical Investigator Communicable Diseases Complex Coronary DNA Data Development Diagnosis Dietary Factors Dietary Intervention Dietary intake Disease Dyslipidemias Environment Environmental Risk Factor Epidemiologic Studies Event Fellowship Funding Future General Population Genes Genetic Genetic Determinism Genetic Polymorphism Genetic Variation Genetic screening method Genotype Goals Guidelines HIV HIV Infections HIV Seropositivity HIV-Associated Lipodystrophy Syndrome Highly Active Antiretroviral Therapy Incidence Indinavir Individual Infection Insulin Resistance Intervention K-Series Research Career Programs Knowledge Lead Learning Link Lipids Longitudinal Studies Lopinavir/Ritonavir Mentored Patient-Oriented Research Career Development Award Mentors Metabolic Metabolic syndrome Morbidity - disease rate Nutritional status Outcome Participant Patient Care Patients Pattern Peroxisome Proliferator-Activated Receptors Persons Pharmaceutical Preparations Pharmacogenetics Phenotype Plasma Play Population Predisposition Prevention strategy Principal Investigator Public Health Qualifying Recommendation Research Research Personnel Risk Risk Factors Ritonavir Role Sampling Stavudine Stratification Supervision Surrogate Markers Techniques Tenofovir Testing Thick Translating Treatment Protocols Variant adiponectin antiretroviral therapy apolipoprotein E-1 atherogenesis cardiovascular risk factor career career development clinical epidemiology cohort design genetic analysis genetic epidemiology genetic risk factor high risk innovation intima media lipoprotein lipase mortality novel nutrition patient oriented patient oriented research perilipin premature premature atherosclerosis prevent programs response skills tool treatment effect

展开

项目摘要

DESCRIPTION (provided by applicant): The overall scientific goal of this proposal is to determine how host genetic factors relate to adverse effects commonly observed in HIV infection. To achieve this goal, we will analyze DNA samples extracted from participants of a previously established cohort of 327 HIV-infected patients from a large longitudinal study that examines nutritional status in HIV infection. Polymorphisms in the genes commonly linked to metabolic and morphologic abnormalities in the general population will be determined in HIV-positive individuals. Specifically, this proposal aims at examining the association of seven selected candidate genes with incidence and rate of progression of carotid intima-media thickness and coronary calcium scores, and with the presence of metabolic syndrome, all surrogate markers of future cardiovascular events. Finally, dietary intake and individual antiretroviral medications will be assessed for their interaction with candidate genes. We hypothesize that genetic mechanisms confer susceptibility to the development of metabolic and morphologic complications in HIV-infected individuals treated with selective antiretroviral regimens, since these complications do not occur in all exposed patients. This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting clinical and epidemiologic research under the supervision of an advisory committee comprised of highly qualified mentors in an environment ideally suited for the study of HIV disease and genetic analysis. Through coursework, seminars and supervised research, the PI will gain knowledge and expertise in techniques pertinent to the proposed research. This K23 award in combination with the PI's background in infectious diseases, nutrition, clinical epidemiology and biostatistics, will provides excellent potential for the development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complications in HIV infection. At the end of the award, the PI will be a competitive applicant for R01 funding. PUBLIC HEALTH IMPLICATIONS: The proposed study has significant clinical and public health implications as the results may affect the choice of future antiretroviral medications, dietary interventions, risk stratification guidelines and preventive strategies to avoid the metabolic and morphologic complications observed with HIV disease and its treatment, and may lead to directed interventions in the care of patients.

描述（由申请人提供）：该提案的总体科学目标是确定宿主遗传因素与HIV感染中通常观察到的不良反应的关系。为了实现这一目标，我们将分析从一项大型纵向研究中研究的327例HIV感染患者的参与者中提取的DNA样本，该研究检查了HIV感染中的营养状况。在HIV阳性个体中，将确定与一般人群中代谢和形态异常相关的基因中的多态性。具体而言，该提案旨在研究七个选定的候选基因的关联，并与颈动脉内膜厚度和冠状动脉钙评分的发生率和进展率，以及代谢综合征的存在，所有这些都是未来心血管事件的替代标记。最后，将评估饮食摄入量和个体抗逆转录病毒药物与候选基因的相互作用。我们假设遗传机制赋予了用选择性抗逆转录病毒治疗治疗的HIV感染个体中代谢和形态并发症发展的敏感性，因为这些并发症均未发生在所有暴露的患者中。该建议旨在为首席研究人员（PI）提供机会，以在一个由高素质的导师组成的咨询委员会的监督下，在适合于艾滋病毒疾病和遗传分析的研究中，在一个高素质的咨询委员会的监督下，在设计和进行临床和流行病学研究方面获得知识和技能。通过课程，研讨会和监督研究，PI将获得与拟议研究有关的技术知识和专业知识。这项K23奖与PI在传染病，营养，临床流行病学和生物统计学方面的背景相结合，将为开发成功的独立研究职业提供巨大的潜力，这些研究专注于以患者为导向的研究研究中，研究了HIV感染中并发症的遗传流行病学。在奖励结束时，PI将成为R01资金的竞争申请人。公共卫生的影响：拟议的研究具有重大的临床和公共卫生影响，因为结果可能会影响未来的抗逆转录病毒药物，饮食干预措施，风险分层指南和预防策略，以避免避免使用HIV疾病及其治疗的代谢和形态并发症，并可能导致对患者护理的有效干预措施。