title: Efficacy of ezetimibe is not related to NPC1L1 gene polymorphisms in a pilot study of Chilean hypercholesterolemic subjects.
abstract: OBJECTIVE
  Niemann-Pick C1 Like 1 (NPC1L1) is a multi-transmembrane transport protein highly expressed in the small intestine. It mediates sterol transfer throughout the brush border membrane of enterocytes, becoming essential for intestinal cholesterol absorption and ensuing whole-body cholesterol homeostasis. This protein is targeted by ezetimibe, a potent cholesterol absorption inhibitor. Single nucleotide polymorphisms (SNPs) in NPC1L1 have been associated to variation in both plasma low-density lipoprotein (LDL) cholesterol levels and lipid-lowering medication with ezetimibe. However, there are no data evaluating the impact of NPC1L1 variants on Chilean subjects medicated with ezetimibe monotherapy. Therefore, we assessed the contribution of two unexplored NPC1L1 variants on plasma lipids and response to ezetimibe in Chilean hypercholesterolemic individuals.
  
  
  METHODS
  Using PCR-restriction fragment length polymorphism (RFLP), we analyzed the SNP distribution of two common variants; -133A>G (rs17655652) and 1679C>G (rs2072183), and their relation with plasma lipids and lipid-lowering response to ezetimibe in 60 hypercholesterolemic Chilean subjects.
  
  
  RESULTS
  Genotype distribution for the rs17655652 variant was AA 57 %, 40 % AG and 3 % GG, whereas for the rs2072183 SNP was 57 % CC, 35 % CG and 8 % GG. Minor allele frequencies (MAFs) were 0.23 and 0.26, respectively. No association was observed between NPC1L1 SNPs and baseline cholesterol. After therapy, none of the polymorphisms affected ezetimibe response in the studied cohort (P > 0.05).
  
  
  CONCLUSIONS
  Data obtained indicates that polymorphisms rs17655652 and rs2072183 were not related to cholesterol variability. Also, lipid-lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms studied in Chilean hypercholesterolemic subjects.
authors.affiliation: Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Tomás
authors.initials: T
authors.lastname: Zambrano
authors.forename: Nicolás
authors.initials: N
authors.lastname: Saavedra
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.forename: José
authors.initials: J
authors.lastname: Caamaño
authors.forename: Luis A
authors.initials: LA
authors.lastname: Salazar
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D002677:Chile; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D000069438:Ezetimibe