3′UTR/T polymorphism of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with modified anti-platelet activity of atorvastatin in hypercholesterolemic subjects

Oxidized-low density lipoproteins (ox-LDL) and the specific receptor LOX-1 are involved in atherogenesis and atherothrombosis. LOX-1 downregulation is associated with the anti-platelet action of atorvastatin. 3′UTR/T LOX-1 polymorphism has been associated with increased risk of coronary artery disease. This study was planned to determine whether LOX-1 genetic variations could affect anti-platelet action of atorvastatin. We studied by platelet P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection) whether differences in cellular activation could be suitable in 109 3′UTR/T carriers out of 201 hypercholesterolemic subjects treated with atorvastatin 20 mg/day. Hyperactivated platelets (P-sel in resting cells and % variation upon thrombin activation, p < 0.001) were detected at baseline in patients without significant differences between T or C carriers. P-sel and platelet-associated ox-LDL, were significantly decreased (all p < 0.001) in C carriers after one week of treatment before LDL reduction. In 3′UTR/T carriers P-sel was reduced (p < 0.01) after 6 weeks of treatment according to LDL and ox-LDL reduction. In 3′UTR/T carriers atorvastatin reduced platelet activity by LDL and ox-LDL lowering and not by rapid CD36 and LOX-1 downregulation as in C carriers. Such data suggest that in T carriers LDL lowering is needed to achieve anti-platelet action.