Pharmacogenomics and Hypertension

药物基因组学和高血压

基本信息

批准号：
7636825
负责人：
VIBHA BHATNAGAR
金额：
$ 9.94万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2006-07-15 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7636825
关键词：
ADRB1 gene ADRB2 gene Adrenergic beta-Antagonists Age Alcohol consumption Amino Acids Analysis of Variance Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Bioinformatics Blood Pressure California Candidate Disease Gene Catecholamines Clinical Complex Computer software Congestive Heart Failure DNA Databases Development Diagnosis Diet Down-Regulation Drug Delivery Systems Drug Kinetics Environment Essential Hypertension Ethnic Origin Ethnic group Exons Frequencies Functional disorder Gender Gene Frequency Genes Genetic Genetic Code Genetic Polymorphism Genetic Transcription Genome Genomics Genotype Haplotypes Healthcare Systems Hypertension Inborn Genetic Diseases Individual Insulin Insulin Resistance Introns Kidney Kidney Diseases Link Logistic Regressions Manuscripts Measures Medical Medical Records Mentors Metabolic Pathway Metabolic syndrome Minor Modeling Modification Multivariate Analysis Non-Insulin-Dependent Diabetes Mellitus Obesity Online Mendelian Inheritance In Man Pathway interactions Patient Care Patients Pharmaceutical Preparations Pharmacodynamics Pharmacogenetics Pharmacogenomics Phenotype Population Study Prevalence Primary Health Care Process Promoter Regions Public Health Schools Publications Publishing Receptor Gene Recruitment Activity Regression Analysis Regulation Research Research Personnel Role Sample Size Smoking Staging Stratification Substance abuse problem Surveys Testing Thiazide Diuretics Thyroid Diseases Training Translating Universities Variant Weight Work Writing base beta-adrenergic receptor career clinical application clinical epidemiology clinically relevant cohort compliance behavior interest lifestyle factors man patient population post-doctoral training professor programs promoter receptor response salt intake thiazide trait volunteer

项目摘要

DESCRIPTION (provided by applicant): This is a revised application by Dr. Bhatnagar, an MD, MPH in the early stages of establishing a research career in clinical epidemiology, with a focus on pharmacogenetic predictors of antihypertensive drug response. She has completed an MPH degree from the Harvard School of Public Health (1999), continued post-doctoral training in clinical epidemiology at the University of California San Diego (UCSD) (2000 to2002), and has now established a primary care hypertensive patient cohort (N=1,502) from the VA San Diego Healthcare System (2003-2005). She has several first authored primary research publications and, since the last submission, has written three first-authored research manuscripts directly related to this proposal (one recently published and two in review). She will be developing a comprehensive medical genomic database. Patients on monotherapy for hypertension- ie. angiotensin converting enzyme inhibitor, beta adrenergic receptor blocker or thiazide diuretic-will be genotyped at specific candidate genetic loci and the association between drug response (blood pressure response) and genoype will be measured (ANOVA).Logistic regression analyses will be used to control for other predictors of drug response. Haplotype analyses will focus on teasing out the contribution of multiple polymorphisms on a gene, as well as uncover the contribution of a gene region to drug response. A sample size of about 200 patients per monotherapy group will be adequate to detect moderate effect sizes (moderate differences in response rates) between patients with and without common polymoprhisms (minor allele frequency over 15%). Only common polymorphisms in this patient population will be studied because the investigator is interested in the clinical applications of genotype testing to patient care. The training portion will focus on: 1) didactic coursework in medical genomics; 2) lab training in DNA quantification and processing; and 3) training in bioinformatics and database development, and the use of software programs for genomic analyses. Dr. Bhatnagar will be working in a rich environment under successful senior UCSD investigators: 1) Mentor - Dr. Daniel T. O'Connor (Chief of Hypertension, investigator in pharmacogenomics and hypertension pathophysiology); 2) Co-mentor - Dr. Sanjay K. Nigam (Professor, investigator in renal drug handling); and 3) Biostatistical consultant - Dr. Nicholas J. Schork (Professor, expertise in statistical genomics).

描述（由申请人提供）：这是 Bhatnagar 博士的修订申请，Bhatnagar 博士是医学博士、公共卫生硕士，处于临床流行病学研究生涯的早期阶段，重点关注抗高血压药物反应的药物遗传学预测因子。她已获得哈佛大学公共卫生学院的公共卫生硕士学位（1999 年），并在加州大学圣地亚哥分校 (UCSD) 继续接受临床流行病学博士后培训（2000 年至 2002 年），现已建立了初级保健高血压患者队列(N=1,502) 来自 VA 圣地亚哥医疗系统 (2003-2005)。她拥有几篇第一作者的主要研究出版物，自上次提交以来，她撰写了三篇与该提案直接相关的第一作者研究手稿（一篇最近发表，两篇正在审稿中）。她将开发一个全面的医学基因组数据库。接受单一疗法治疗高血压的患者 - 即。血管紧张素转换酶抑制剂、β肾上腺素能受体阻滞剂或噻嗪类利尿剂——将在特定候选基因位点进行基因分型，并测量药物反应（血压反应）和基因型之间的关联（方差分析）。逻辑回归分析将用于控制药物反应的其他预测因素。单倍型分析将侧重于梳理基因上多个多态性的贡献，以及揭示基因区域对药物反应的贡献。每个单一治疗组约 200 名患者的样本量足以检测具有和不具有常见多态性（次要等位基因频率超过 15%）的患者之间的中等效应大小（反应率的中等差异）。仅研究该患者群体中常见的多态性，因为研究者对基因型测试在患者护理中的临床应用感兴趣。培训部分将重点关注：1）医学基因组学教学课程； 2）DNA定量和处理的实验室培训； 3) 生物信息学和数据库开发以及基因组分析软件程序的使用培训。 Bhatnagar 博士将在 UCSD 成功的高级研究人员的领导下在一个丰富的环境中工作： 1) 导师 - Daniel T. O'Connor 博士（高血压科主任，药物基因组学和高血压病理生理学研究人员）； 2) 共同导师 - Sanjay K. Nigam 博士（教授，肾脏药物处理研究人员）； 3) 生物统计顾问 - Nicholas J. Schork 博士（教授，统计基因组学专业知识）。