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). ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR020822-03
Application #
7478011
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2006-07-15
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$105,992
Indirect Cost
Name
University of California San Diego
Department
Family Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Bhalla, M; Aziz, H; Richard, E et al. (2013) Serum potassium predicts time to blood pressure response among African Americans with hypertensive nephrosclerosis. J Hum Hypertens 27:393-6
Bhatnagar, Vibha; Liu, Lin; Nievergelt, Caroline M et al. (2012) Paraoxonase 1 (PON1) C/T-108 association with longitudinal mean arterial blood pressure. Am J Hypertens 25:1188-94
Lee, Jason; Aziz, Hossein; Liu, Lin et al. (2011) ?(1)-adrenergic receptor polymorphisms and response to ?-blockade in the African-American study of kidney disease and hypertension (AASK). Am J Hypertens 24:694-700
Bhatnagar, Vibha; Garcia, Erin P; O'Connor, Daniel T et al. (2010) CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol 31:95-103
Salem, Rany M; Pandey, Braj; Richard, Erin et al. (2010) The VA Hypertension Primary Care Longitudinal Cohort: Electronic medical records in the post-genomic era. Health Informatics J 16:274-86
Bhatnagar, Vibha; O'Connor, Daniel T; Brophy, Victoria H et al. (2009) G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions. Am J Hypertens 22:332-8
Ahn, Sun-Young; Bhatnagar, Vibha (2008) Update on the molecular physiology of organic anion transporters. Curr Opin Nephrol Hypertens 17:499-505
Bhatnagar, Vibha; O'Connor, Daniel T; Schork, Nicholas J et al. (2007) Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial. J Hypertens 25:2082-92