Sequence variation in NPC1L1 and association with improved LDL-cholesterol lowering in response to ezetimibe treatment - PubMed (original) (raw)
Comparative Study
doi: 10.1016/j.ygeno.2005.08.007. Epub 2005 Nov 16.
Maha C Karnoub, David J Devlin, Maria G Arreaza, Ping Qiu, Stephanie A Monks, Michael E Severino, Paul Deutsch, Joanne Palmisano, Alan B Sachs, Marvin L Bayne, Andrew S Plump, Eric E Schadt
Affiliations
- PMID: 16297596
- DOI: 10.1016/j.ygeno.2005.08.007
Free article
Comparative Study
Sequence variation in NPC1L1 and association with improved LDL-cholesterol lowering in response to ezetimibe treatment
Jason S Simon et al. Genomics. 2005 Dec.
Free article
Abstract
Niemann-Pick C1-like 1 (NPC1L1) is an intestinal cholesterol transporter and the molecular target of ezetimibe, a cholesterol absorption inhibitor demonstrated to reduce LDL-cholesterol (LDL-C) both as monotherapy and when co-administered with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Interestingly, significant interindividual variability has been observed for rates of intestinal cholesterol absorption and LDL-C reductions at both baseline and post ezetimibe treatment. To test the hypothesis that genetic variation in NPC1L1 could influence the LDL-C response to ezetimibe, we performed extensive resequencing of the gene in 375 apparently healthy individuals and genotyped hypercholesterolemic patients from clinical trial cohorts. No association was observed between NPC1L1 single-nucleotide polymorphism and baseline cholesterol. However, significant associations to LDL-C response to treatment with ezetimibe were observed in patients treated with ezetimibe in two large clinical trials. Our data demonstrate that DNA sequence variants in NPC1L1 are associated with an improvement in response to ezetimibe pharmacotherapy and suggest that detailed analysis of genetic variability in clinical trial cohorts can lead to improved understanding of factors contributing to variable drug response.
Similar articles
- Efficacy of ezetimibe is not related to NPC1L1 gene polymorphisms in a pilot study of Chilean hypercholesterolemic subjects.
Zambrano T, Saavedra N, Lanas F, Caamaño J, Salazar LA. Zambrano T, et al. Mol Diagn Ther. 2015 Feb;19(1):45-52. doi: 10.1007/s40291-014-0128-x. Mol Diagn Ther. 2015. PMID: 25589339 - Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia.
Davis HR, Veltri EP. Davis HR, et al. J Atheroscler Thromb. 2007 Jun;14(3):99-108. doi: 10.5551/jat.14.99. J Atheroscler Thromb. 2007. PMID: 17587760 Review. - Gene polymorphism and frequencies of the NPC1L1 gene (rs2072183, rs217434 and rs217428) in Japanese patients with dyslipidemia.
Kashiwabara Y, Kobayashi Y, Koba S, Kohyama N, Ohbayashi M, Murayama JI, Hirano T, Kobayashi Y, Yamamoto T. Kashiwabara Y, et al. J Clin Pharm Ther. 2014 Oct;39(5):551-4. doi: 10.1111/jcpt.12176. Epub 2014 May 26. J Clin Pharm Ther. 2014. PMID: 24861377 - In vivo responsiveness to ezetimibe correlates with niemann-pick C1 like-1 (NPC1L1) binding affinity: Comparison of multiple species NPC1L1 orthologs.
Hawes BE, O'neill KA, Yao X, Crona JH, Davis HR Jr, Graziano MP, Altmann SW. Hawes BE, et al. Mol Pharmacol. 2007 Jan;71(1):19-29. doi: 10.1124/mol.106.027896. Epub 2006 Sep 27. Mol Pharmacol. 2007. PMID: 17005902 - Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport.
Jia L, Betters JL, Yu L. Jia L, et al. Annu Rev Physiol. 2011;73:239-59. doi: 10.1146/annurev-physiol-012110-142233. Annu Rev Physiol. 2011. PMID: 20809793 Free PMC article. Review.
Cited by
- Potential impact of ezetimibe on patients with NAFLD/NASH: a meta-analysis of randomized controlled trials.
Jiao B, Wang B, Liu B, Zhao J, Zhang Y. Jiao B, et al. Front Endocrinol (Lausanne). 2024 Oct 8;15:1468476. doi: 10.3389/fendo.2024.1468476. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 39439571 Free PMC article. - NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.
Cho D, Huang X, Han Y, Kim M. Cho D, et al. Biochem Genet. 2024 Oct;62(5):4103-4119. doi: 10.1007/s10528-023-10649-6. Epub 2024 Jan 27. Biochem Genet. 2024. PMID: 38280151 - Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk.
Mauriello A, Ascrizzi A, Molinari R, Falco L, Caturano A, D'Andrea A, Russo V. Mauriello A, et al. Genes (Basel). 2023 Nov 9;14(11):2057. doi: 10.3390/genes14112057. Genes (Basel). 2023. PMID: 38003001 Free PMC article. Review. - Computationally Modelling Cholesterol Metabolism and Atherosclerosis.
Davies C, Morgan AE, Mc Auley MT. Davies C, et al. Biology (Basel). 2023 Aug 14;12(8):1133. doi: 10.3390/biology12081133. Biology (Basel). 2023. PMID: 37627017 Free PMC article. - A Jordanian Multidisciplinary Consensus Statement on the Management of Dyslipidemia.
Al Mousa E, Al-Azzam S, Araydah M, Karasneh R, Ghnaimat M, Al-Makhamreh H, Al Khawaldeh A, Ali Abu Al-Samen M, Haddad J, Al Najjar S, Alsalaheen Abbadi H, Hammoudeh AJ. Al Mousa E, et al. J Clin Med. 2023 Jun 27;12(13):4312. doi: 10.3390/jcm12134312. J Clin Med. 2023. PMID: 37445345 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical