Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin

Statin therapy, although generally well tolerated, leads not infrequently to significant subjective and at times objective adverse effects (AEs), mainly of a muscular nature. The genetic background of these AEs is not clear and possibly side effects and lipid lowering efficacy may be linked. Aim of the study was a detailed evaluation of CYP450 and apolipoprotein E gene polymorphisms in two large series of age-sex matched patients with and without muscular side effects to statins. In a Clinical Institution specialised in lipid-lipoprotein disorders, 50 statin treated patients were selected, with subjective or objective statin-associated myopathy, evaluated using standardized forms. These were sex and age matched with 50 statin-treated patients from the same Clinic, without any subjective or objective complaints. DNA samples for the evaluation of CYP450 genetic polymorphisms and apo E genotypes were collected in order to assess correlations with both genetic polymorphisms and AEs, as well as with therapeutic efficacy. None of the assessed CYP450 polymorphisms appeared to be related to an increased incidence of AEs. The CYP2D6 *1/*4 and *4/4* poor metabolizer (PM) status was associated to a higher efficacy of statins metabolized by this system and, in addition, the apo E2 genotype was, in this series, linked to increased HDL-C levels after therapy. Patients with statin associated myopathy are not characterized by significantly different genotypes for the CYP450s responsible for statin metabolism. On the other hand, CYP2D6 PM status is associated to an increased efficacy of statins metabolized by this system.