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Mammalian protein found in Homo sapiens
Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract's epithelial cells[ 5] hepatocytes .[ 6] mediator of cholesterol absorption.
The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption , resulting in a blood cholesterol reduction of 15-20%.[ 7] Polymorphic variations in the NPC1L1 gene could be associated with non-response to ezetimibe treatment.[ 8] inactivating mutations in the NPC1L1 gene had a lower LDL cholesterol level , as well as an around 50% reduction in the risk of coronary heart disease .[ 9]
NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.[ 10]
As cancer appeared more frequently in patients treated with simvastatin -ezetimibe combination therapy in one clinical trial,[ 11] hypothesized that NPC1L1 by ezetimibe might be associated with an increased cancer risk.[ 12] meta-analysis of ezetimibe clinical data showed no increase in the risk of cancer from treatment with ezetimibe.[ 13]
^ a b c GRCh38: Ensembl release 89: ENSG00000015520 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020447 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)" . Proceedings of the National Academy of Sciences of the United States of America . 102 (23): 8132–7. Bibcode :2005PNAS..102.8132G . doi :10.1073/pnas.0500269102 PMC 1149415 PMID 15928087 . ^ Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe" . The Journal of Clinical Investigation . 117 (7): 1968–78. doi :10.1172/JCI30060 . PMC 1888567 PMID 17571164 . ^ Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia" . Journal of Atherosclerosis and Thrombosis . 14 (3): 99–108. doi :10.5551/jat.14.99 PMID 17587760 . ^ Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt . ^ ^ Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor" . Nature Medicine . 18 (2): 281–5. doi :10.1038/nm.2581 . PMC 3530957 PMID 22231557 . ^ Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis" . The New England Journal of Medicine . 359 (13): 1343–56. doi :10.1056/NEJMoa0804602 PMID 18765433 . ^ Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials" . The New England Journal of Medicine . 359 (13): 1357–66. doi :10.1056/NEJMsa0806603 PMID 18765432 . ^ Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology . 201 : 247–52. doi :10.1016/j.ijcard.2015.08.103 . PMID 26301648 .
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