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Member Research & Reports

Member Research & Reports

UAB Studies Effects of AGT Polymorphisms on Coronary Heart Disease

Previous studies have reported that risk of cardiovascular morbidity and mortality substantially increases in hypertensive patients, especially among those with inadequate blood pressure control. Two common antihypertensive drug classes including thiazide diuretics and angiotensinogen converting enzyme (ACE) inhibitors affect different enzymes in the renin angiotensinogen aldosterone system (RAAS). In the RAAS, angiotensinogen is converted into angiotensin II which increases blood pressure through vasoconstriction.


[Photo: Ms. Anh N. Do]

Using a case-only design with 3,448 high-risk hypertensive individuals from the Genetics of Hypertension Associated Treatment (GenHAT) study, Ms. Anh N. Do, doctoral student, collaborating with Dr. Donna K. Arnett, professor and chair, both in the department of epidemiology at the University of Alabama at Birmingham—in addition to department colleagues Dr. Ryan Irvin, assistant professor; and Dr. Amy I. Lynch, research associate—recently examined whether seven single nucleotide polymorphisms (SNPs) in the angiotensinogen gene (AGT) interact with three classes of antihypertensive drugs including chlorthalidone (a thiazide diuretic), lisinopril (an ACE inhibitor), and amlodipine (a calcium channel blocker) to modify the risk of incident coronary heart disease (CHD) and heart failure (HF) among Caucasian and African American participants, separately.

The researchers found no gene by treatment interactions to be statistically significant after correction for multiple testing; however, some suggestive results were found. African American participants with the minor allele of rs11122576 had over two-fold higher risk of CHD when using chlorthalidone compared with using amlodipine, or lisinopril compared with amlodipine. Other marginal associations are also reported among both race groups.

Study findings suggest that rs11122576 could contribute to future personalization of antihypertensive treatment among African Americans, although the team concluded that more studies are needed.

“The Effects of Angiotensinogen Gene Polymorphisms on Cardiovascular Disease Outcomes during Antihypertensive Treatment in the GenHAT Study” was published in August 2014 in the journal Frontiers in Pharmacology.

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