Personalized Cardiology - Applications of Biotechnology in Cardiovascular Therapeutics - page 331

optimization of LDL-C reduction with minimal risk. The organic anion transporting
polypeptide-1B1 encoded by the SLCO1B1 gene is implicated as a major trans-
porter in cellular uptake of statins, and notably fluvastatin. Results of a pharmacog-
enomics study on elderly subjects with hypercholesterolemia reveal that OATP1B1
gene is implicated in the pharmacological action and efficacy of fluvastatin
(Couvert et al. 2008 ). The common *14 allele of SLCO1B1, which is distinguished
by the presence of the c.463 C > A polymorphism, was associated with enhanced
lipid-lowering efficacy in this study.
Personalized Management of Women with Hyperlipidemia
A study conducted by Genaissance Pharmaceuticals (taken over by Clinical Data)
on individuals who were candidates for statin therapy suggests that women with a
genetic predisposition to protective levels of C-reactive protein (CRP, an estab-
lished marker for fatal coronary disease) lose that benefit when taking hormone
replacement therapy (Judson et al. 2004 ). The results of this study are the first
published result from Genaissance's STRENGTH study described in the preceding
section.
Several studies by leading academic/medical centers have shown that CRP lev-
els may be more important than cholesterol levels for predicting cardiovascular
events such as heart attacks. In particular, these studies have shown that elevated
CRP is a risk factor that is independent of cholesterol levels. It had previously been
shown that HRT caused elevated levels of CRP and heart attacks and strokes
(Women's Health Initiative). The current study shows that the protective effect of a
key genetic variant may be overwhelmed by the use of these drugs.
The results give lifestyle guidance to women who would like to preserve the
protective benefits conferred by favorable genetic variations, and may ultimately
lead to new or modified drugs. The study showed that men and women with com-
mon variants in the apolipoprotein E (APOE) gene on average have naturally lower
levels of CRP. In the case of women, however, the study indicates that this benefi-
cial effect may be largely neutralized by HRT, allowing CRP levels to potentially
increase to dangerous levels.
Thrombotic Disorders
A number of thrombotic disorders cause cardiovascular disease. Venous thrombosis
has an annual incidence of 1 per 1,000 in the general population and is associated
with significant morbidity and mortality. Several genetic variants have been identi-
fied that are associated with an increased risk of venous thrombosis, including a
recently discovered mutation in the prothrombin gene. Factor V Leiden mutation is
associated with 15-20% of the cases of idiopathic thrombotic disorders.