Efeito farmacogenético do polimorfismo Ala16Val do gene da MnSOD na resposta de pacientes hipercolesterolêmicos a rosuvastatina

Abstract

Rosuvastatin is used as a drug of first choice in treating hypercholesterolemia due to competitive inhibition of HMG-CoA reductase enzyme which converts HMG-CoA to mevalonic acid which is the rate-limiting step in cholesterol synthesis, also attenuates the inflammatory process and oxidative, mainly by reducing the production of superoxide anion. Superoxide anion is metabolized by manganese-dependent superoxide dismutase (MnSOD or SOD2) that act into mitochondria. In humans, there is a gene polymorphism where a valine (Val) to alanine (Ala) substitution occurs at the 16th amino acid (Ala16Val-SOD2). This polymorphism having two alleles A and V, resulting in three possible genotypes: AA, AV and VV. The VV genotype has been associated with the risk of developing several metabolic diseases, such as hypercholesterolemia. Thus, in order to further explore this phenomenon , this study investigated the influence of Ala16Val - SOD2 polymorphism on lipid profile and inflammatory and fibrinolytic biomarkers of 122 hypercholesterolemic patients treated with 20 mg of rosuvastatin for 120 days. The results indicated that patients with the VV genotype showed a lower response to rosuvastatin, compared with patients with the AA and AV genotypes. The effects of rosuvastatin in inflammatory and fibrinolytic biomarkers were also milder in these patients. These results suggest some effects of pharmacogenetic - SOD2 Ala16Val polymorphism in the treatment of hypercholesterolemia.