title: Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.
abstract: 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.
  
  
  OBJECTIVE
  To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention.
  
  
  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 undesirable 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.
authors.affiliation: Department of Clinical Medicine and Immunology, Internal Medicine Division, Center for Atherosclerosis Research, Policlinico Le Scotte, University of Siena, V.le Bracci, 53100, Siena, Italy. puccetti@unisi.it
authors.forename: L
authors.initials: L
authors.lastname: Puccetti
authors.forename: A L
authors.initials: AL
authors.lastname: Pasqui
authors.forename: F
authors.initials: F
authors.lastname: Bruni
authors.forename: M
authors.initials: M
authors.lastname: Pastorelli
authors.forename: F
authors.initials: F
authors.lastname: Ciani
authors.forename: A
authors.initials: A
authors.lastname: Palazzuoli
authors.forename: A
authors.initials: A
authors.lastname: Pontani
authors.forename: A
authors.initials: A
authors.lastname: Ghezzi
authors.forename: A
authors.initials: A
authors.lastname: Auteri
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000008:administration & dosage*; D012189:Retrospective Studies; D012307:Risk Factors; D051127:Scavenger Receptors, Class E / Q000235:genetics*; D019821:Simvastatin / Q000008:administration & dosage; D013927:Thrombosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; C495137:OLR1 protein, human; D011758:Pyrroles; D051127:Scavenger Receptors, Class E; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin