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Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia

L Puccetti1, F Bruni, A L Pasqui

  • 1Department of Clinical Medicine and Immunology, Internal Medicine Division, Centre for Atherosclerosis Research, University of Siena, Siena, Italy. puccetti@unisi.it

European Journal of Clinical Investigation
|January 5, 2008
PubMed

Insights

Genetic variations in LOX-1 influence statin effectiveness for coronary artery disease (CAD) prevention. These polymorphisms may enhance antithrombotic mechanisms beyond lipid reduction, improving cardiovascular event outcomes.

Area of Science:

  • Cardiovascular Genetics
  • Pharmacogenomics
  • Thrombosis Research

Background:

  • Statins may provide cardiovascular benefits through mechanisms beyond lipid lowering, including antithrombotic actions.
  • Genetic factors, such as polymorphisms in oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS), influence these effects.
  • Investigating these genetic influences is crucial for optimizing statin therapy in coronary artery disease (CAD) patients.

Purpose of the Study:

  • To evaluate the impact of ox-LDL lectin-like receptor-1 (LOX-1) and NOS gene polymorphisms on cardiovascular event incidence.
  • To assess the role of these polymorphisms in hypercholesterolemic subjects undergoing statin treatment.
  • To determine if genetic factors modify the effectiveness of statins in preventing cardiovascular events.

Main Methods:

  • A prospective 4-year study of 1039 event-free hypercholesterolemic subjects treated with atorvastatin.
  • Detection of LOX-1 3'UTR/T-C and NOS G894T polymorphisms using polymerase chain reaction-based assays.
  • Measurement of lipid profile, ox-LDL levels, platelet activation (P-selectin expression), NOS activity, and C-reactive protein.

Main Results:

  • The LOX-1 3'UTR/T polymorphism showed a strong association with cardiovascular events (OR 4.90, P < 0.00001), independent of LDL reduction.
  • Smoking significantly influenced event incidence in LDL-targeted subjects (P < 0.0001).
  • Ox-LDL and P-selectin levels were better indicators of risk than LDL in subjects with the 3'UTR/C genotype (OR 4.21, P < 0.0001).

Conclusions:

  • LOX-1 polymorphisms appear to influence statin effectiveness in CAD prevention.
  • These genetic variations may enhance statin efficacy by increasing sensitivity to antithrombotic mechanisms, such as antiplatelet activity.
  • Genetic profiling could personalize statin therapy for improved cardiovascular event prevention.
Abstract

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