Genetic factors in the progression of atherosclerosis and response to cholesterol lowering drugs

Generic factors play a role in the development of atherosclerosis. While some monogenetic disorders induce premature atherosclerosis, other genetic alterations cooperate in a polygenetic model, modifying the process of atherosclerosis. Genetic alterations can modify disease but can also modify the efficacy of treatment of the disease. An example of such a modifying gene is the deletion polymorphism in the 16th intron of the angiotensin converting enzyme (ACE) gene. This polymorphism is associated with higher ACE activities, and a broad variety of diseases. We assessed in a subset of the REgression GRowth Evaluation Statin Study (REGRESS) whether the ACE gene polymorphism modifies the beneficial effect of pravastatin on the atherosclerotic process. We found that the lipid lowering effect of pravastatin was similar to the three genotype groups. However, the effect of the lipid lowering drugs pravastatin on the progression of coronary at atherosclerosis was attenuated in the DID genotype group. This demonstrates that the ACE deletion genotype can modify the response to treatment. Therefore, involvement of generic alterations in modifying disease and therapy should reserve the treatment of cardiovascular disorders from a population and evidence-based approach, towards an individual-based intervention.