Clinical trial NCT00563901: Analyzing How Genetics May Affect Response to High Blood Pressure Medications
Official title: GenHAT - Genetics of Hypertension Associated Treatments - Ancillary to ALLHAT
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension
Coronary Disease
Cerebrovascular Accident
Keywords: CHD
Combined CHD
Stroke
Combined Cardiovascular Disease (CVD)
Pharmacogenetics
End-Stage Renal Disease
Heart Failure
Hospitalized/Fatal Heart Failure
Angina
Coronary Revascularizations
CHD Mortality
Lisinopril
Chlorthalidone
Amlodipine
Doxazosin
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Texas
name: University of Minnesota
First posted: 2007-11-26
Enrollment: 37939
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population samples will be taken from adults who are high risk for high blood pressure in the ALLHAT study, which included a randomized trial of the four high blood pressure drugs chlorthalidone, amlodipine, lisinopril, and doxazosin.

Brief 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.

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 criteria: Inclusion Criteria:

* Participant in the ALLHAT study

Primary outcomes:
measure: Candidate genes that interact with ALLHAT high blood pressure medications to modify risk of other cardiovascular conditions
timeFrame: Measured at completion of genetic analysis
Secondary outcomes:
measure: Within selected candidate genes, effect of multiple gene interactions with high blood pressure medications in modifying risk of other cardiovascular conditions
timeFrame: Measured at completion of genetic analysis
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Houston
country: United States
facility: University of Texas Houston
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: Donna K. Arnett, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1038/sj.tpj.6500113.
citation: 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. doi: 10.1002/sim.1831.
citation: Arnett DK, Davis BR, Ford CE, Boerwinkle E, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005 Jun 28;111(25):3374-83. doi: 10.1161/CIRCULATIONAHA.104.504639. Epub 2005 Jun 20.
citation: Davis BR, Arnett DK, Boerwinkle E, Ford CE, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study. Pharmacogenomics J. 2007 Apr;7(2):112-22. doi: 10.1038/sj.tpj.6500395. Epub 2006 May 16.
citation: Maitland-van der Zee AH, Boerwinkle E, Arnett DK, Davis BR, Leiendecker-Foster C, Miller MB, Klungel OH, Ford CE, Eckfeldt JH. Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Am Heart J. 2007 Jan;153(1):54-8. doi: 10.1016/j.ahj.2006.10.019.
citation: Sherva R, Ford CE, Eckfeldt JH, Davis BR, Boerwinkle E, Arnett DK. Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study. Stroke. 2011 Feb;42(2):330-5. doi: 10.1161/STROKEAHA.110.593798. Epub 2010 Dec 23.