Personalized Cardiology - Applications of Biotechnology in Cardiovascular Therapeutics - page 335

complicated by the fact that the electrical activity in every patient's heart is subtly
different. With the aid of a computerized model that reflects the patient's unique
heart structure and function, it may be able to test the results of destroying different
areas of tissue before operating on the patient.

Concluding Remarks

Genetic factors may influence the response to antihypertensive medication. A num-
ber of studies have investigated genetic polymorphisms as determinants of cardio-
vascular response to antihypertensive drug therapy. Hypertensive patients with the
460 W allele of the a-adducin gene have a lower risk of myocardial infarction and
stroke when treated with diuretics compared with other antihypertensive therapies.
With regard to blood pressure response, interactions were also found between
genetic polymorphisms for endothelial nitric oxide synthase (eNOS) and diuretics
and the ACE gene and angiotensin II type 1 receptor antagonists. Although there
are controversies to settle and difficulties to overcome, pharmacogenetics may yield
successful strategies to optimize drug therapy. Several candidate genes are cur-
rently under investigation for their potential to modify response to antihypertensive
drugs. Findings from previous studies require conformation in other studies to be
able to make definitive conclusions about current positive drug-gene interactions.
It is also important that research groups collaborate more in order to facilitate the
conduct of a meta-analysis for conclusive results. With the development of efficient
methods for analyzing massive amounts of data, pharmacogenetic studies may
eventually lead to the optimization of antihypertensive drug therapy based on
genetic profiles of patients.

References

Arking DE, Pfeufer A, Post W, et al. A common genetic variant in the NOS1 regulator NOS1AP
modulates cardiac repolarization. Nat Genetics 2006;38:644-51.
Caulfield T, McGuire AL, Cho M, et al. Research Ethics Recommendations for Whole-Genome
Research: Consensus Statement. PLoS Biology 2008;6:e73 doi:10.1371/journal.

pbio.0060073.
Chasman DI, Posada D, Subrahmanyan L, et al. Pharmacogenetic study of statin therapy and
cholesterol reduction. JAMA 2004;291:2821-7.
Couvert P, Giral P, Dejager S, et al. Association between a frequent allele of the gene encoding
OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy. Pharmacogenomics
2008;9:1217-27.
Ferrandi M, Molinari I, Torielli L, et al. Adducin- and Ouabain-Related Gene Variants Predict the
Antihypertensive Activity of Rostafuroxin, Part 1: Experimental Studies. Sci Transl Med
2010;2:59ra86.
Hakonarson H, Thorvaldsson S, Helgadottir A, et al. Effects of a 5-Lipoxygenase-Activating
Protein Inhibitor on Biomarkers Associated With Risk of Myocardial Infarction:
A Randomized Trial. JAMA 2005;293:2245-2256.
Harrap SB. Where are all the blood-pressure genes? Lancet 2003;361:2149-51.