Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment

Background Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3′UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. Objectives To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. Patients/Methods The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n = 382, 247 male, 135 female) or simvastatin (n = 369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic–colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. Results Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p = 0.175) and sex (p = 0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesiderable LDL) had the 3′UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46–6.70, p < 0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p < 0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p < 0.001) in the whole cohort. Conclusions In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.