Efficacy of Ezetimibe Is Not Related to NPC1L1 Gene Polymorphisms in a Pilot Study of Chilean Hypercholesterolemic Subjects

• Published in: Molecular diagnosis & therapy Vol. 19; no. 1; pp. 45 - 52
• Main Authors: Zambrano, Tomás, Saavedra, Nicolás, Lanas, Fernando, Caamaño, José, Salazar, Luis A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2015; Springer Nature B.V
• Subjects: Adult; Anticholesteremic Agents - therapeutic use; Azetidines - therapeutic use; Bile; Biological Transport - drug effects; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chile; Cholesterol; Cholesterol, LDL - blood; Conflicts of interest; Ezetimibe; Female; Gene Expression; Genes; Genotype; Human Genetics; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Intestinal Absorption - drug effects; Laboratory Medicine; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Molecular Medicine; Original Research Article; Pharmacotherapy; Pilot Projects; Polymorphism, Genetic; Rodents; Treatment Outcome; Chile; Ezetimibe Treatment; Intestinal Cholesterol Absorption; Ezetimibe Monotherapy; Cholesterol Absorption; Ezetimibe
• ISSN: 1177-1062; 1179-2000
• DOI: 10.1007/s40291-014-0128-x

Background and 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). Conclusion 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.