Analyzing How Genetics May Affect Response to High Blood Pressure Medications
Information source: National Heart, Lung, and Blood Institute (NHLBI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Coronary Disease; Cerebrovascular Accident
Phase: N/A
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI) Official(s) and/or principal investigator(s):
Donna K. Arnett, PhD, Principal Investigator, Affiliation: University of Alabama at Birmingham
Summary
High blood pressure is one of the most common health problems in the United States. There are
many medications to treat high blood pressure, but there is a large variance in how people
respond to these medications. It is believed that genetic variations may contribute to the
inconsistent treatment response. This study will use genetic analysis to determine whether
particular genes interact with high blood pressure medications to modify the risk of certain
cardiovascular diseases.
Clinical Details
Official title: GenHAT - Genetics of Hypertension Associated Treatments - Ancillary to ALLHAT
Study design: Cohort, Retrospective
Primary outcome: Candidate genes that interact with ALLHAT high blood pressure medications to modify risk of other cardiovascular conditions
Secondary outcome: Within selected candidate genes, effect of multiple gene interactions with high blood pressure medications in modifying risk of other cardiovascular conditions
Detailed description:
High blood pressure affects nearly one in three individuals in the Unites States. There are
many factors that can cause high blood pressure, including family history and genetic traits,
kidney disease, stress, diabetes, and diet. If left untreated, high blood pressure can
increase one's risk for coronary heart disease (CHD), stroke, heart attack, and heart
failure. While high blood pressure can be managed with medication, people receiving
medication treatment for high blood pressure are still variably at risk for CHD and other
cardiovascular conditions. This risk variation may stem from varying drug reactions that are
likely due to genetics. This study will use genetic analysis to determine whether particular
genes interact with high blood pressure medications to modify the risk of certain
cardiovascular diseases.
This is a continuation study to the antihypertensive and lipid-lowering treatment to prevent
heart attack trial (ALLHAT), which included a randomized trial of the four high blood
pressure drugs chlorthalidone, amlodipine, lisinopril, and doxazosin. Using samples from
ALLHAT participants, this study will analyze the interactions of candidate gene pathways of
relevance with medications from the ALLHAT study. Researchers will examine both single DNA
building blocks and multiple genes in the candidate gene pathways and determine whether their
interaction with the ALLHAT drugs modifies the risk of cardiovascular outcomes. Researchers
will perform genetic analysis on 96 genetic markers using structured association testing
(SAT) and false discovery rate (FDR) methods. These methods will control for population
stratification and multiple testing. Finally, the study will establish a mechanism for other
researchers to continue further analysis of the genetic variants examined in this study.
Eligibility
Minimum age: 55 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Participant in the ALLHAT study
Locations and Contacts
University of Minnesota, Minneapolis, Minnesota 55455, United States
University of Texas Houston, Houston, Texas 77030, United States
Additional Information
Click here for more information on the parent ALLHAT study
Related publications: Arnett DK, Boerwinkle E, Davis BR, Eckfeldt J, Ford CE, Black H. Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study. Pharmacogenomics J. 2002;2(5):309-17. Davis BR, Ford CE, Boerwinkle E, Arnett D, Eckfeldt J, Black H. Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study. Stat Med. 2004 Aug 15;23(15):2413-27.
Starting date: September 2000
Ending date: May 2004
Last updated: March 6, 2008
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