If you suffer from high blood pressure (hypertension) your genotype may influence how well you respond to certain medications, according to an article in the Journal of the American Medical Association (JAMA), January 23rd issue.

Of the 71 million Americans who are known to suffer from at least one type of CVD (cardiovascular disease), at least 65 million have high blood pressure. Only about two-thirds of all hypertension patients have their blood pressure controlled successfully with current treatments, the authors explain. Even though treatments have improved in recent years, a sizeable number of patients are not being treated effectively. Using treatment tailored to a CVD patient’s particular genotype has been an area of focus in recent years – however, there have been no effective therapeutic choices for the clinical setting.

Amy I. Lynch, Ph.D., University of Minnesota, Minneapolis, and team carried out a study to find out whether hypertensive patients with minor atrial natruiretic precursor A (NPPA) genotypes (NPPA G664A and NPPA T2238C) randomized to the diuretic chlorthalidone had different outcomes for CVD measures than patients who were randomized to other types of antihypertensive drugs. According to some previous studies, the NPPA gene may have an impact on the effectiveness of hypertensive medications.

The researchers studied data on 38,462 patients with high blood pressure from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized clinical trial which took place at various centers in the USA and Canada. Genotyping was carried out from February 2004 to January 2005. The patients were selected at random to receive a diuretic (chlorthalidone; n = 13,860), a calcium channel blocker (amlodipine; n = 8,174), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril; n = 8,233), or an alpha-blocker (doxazosin; n = 8,195). They were monitored (followed-up) for 4.9 years (average).

They found evidence of a pharmacogenetic* link of the NPPA T2238C variant to coronary heart disease (CHD), stroke, all-cause death, combined CHD, and combined CVD when they compared the chlorthalidone (diuretic) group with the amlodipine (calcium channel blocker) group, and for stroke when they compared the chlorthalidone group with those receiving amlodipine or lisinopril (ACE inhibitor).

* Pharmacogenetics is the study of how people’s genetic makeup affects their responses to drugs.

The link was consistent for all outcomes. Patients who had one copy or more of the minor C allele had a reduced risk of disease/death when given chlorthalidone compared to those who were given amlodipine (and the amlodipine group plus the lisinopril group for stroke). Patients in the chlorthalidone group with the TT genotype had an elevated risk of disease/death compared to those receiving amlodipine.

The researchers wrote “We also observed a pharmacogenetic association of NPPA T2238 on change in systolic and diastolic blood pressure 6 months after treatment randomization in a similar direction: generally, minor C allele carriers had greater reductions in blood pressure when randomized to chlorthalidone vs. either lisinopril or doxazosin relative to those with the common TT genotype.”

“This study demonstrates the importance (and sometimes paradoxical findings) of pharmacogenetic research; for example, while minor NPPA T2238C allele carriers (as well as the entire study population viewed as a whole) may have had more favorable outcomes when randomized to a diuretic (chlorthalidone), participants with the most common genotype (TT) responded better when assigned to a calcium channel blocker (amlodipine) for some clinical outcomes. Further research is needed to determine the optimal approach for personalizing antihypertensive medication treatment regiments according to genotype information and for achieving the best possible clinical outcomes,” they concluded.

“Pharmacogenetic Association of the NPPA T2238C Genetic Variant With Cardiovascular Disease Outcomes in Patients With Hypertension”
Amy I. Lynch, PhD; Eric Boerwinkle, PhD; Barry R. Davis, MD, PhD; Charles E. Ford, PhD; John H. Eckfeldt, MD, PhD; Catherine Leiendecker-Foster, MS; Donna K. Arnett, PhD
JAMA. 2008;299(3):296-307.
Click here to view abstract online

Written by – Christian Nordqvist