NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibeReport as inadecuate




NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe - Download this document for free, or read online. Document in PDF available to download.

Lipids in Health and Disease

, 4:16

First Online: 12 August 2005Received: 25 July 2005Accepted: 12 August 2005

Abstract

BackgroundNPC1L1 encodes a putative intestinal sterol transporter which is the likely target for ezetimibe, a new type of lipid-lowering medication. We previously reported rare non-synonymous mutations in NPC1L1 in an individual who had no plasma lipoprotein response to ezetimibe. We next hypothesized that common variants in NPC1L1 would underlie less extreme inter-individual variations in the plasma LDL cholesterol response to ezetimibe.

ResultsIn 101 dyslipidemic subjects, we found that NPC1L1 haplotype was significantly associated with inter-individual variation in the response of plasma LDL cholesterol to treatment with ezetimibe for 12 weeks. Specifically, about one subject in eight lacked the common NPC1L1 haplotype 1735C-25342A-27677T and these subjects had a significantly greater reduction in plasma LDL cholesterol with ezetimibe than subjects with at least one copy of this haplotype -35.9+4.0 versus -23.6+1.6 percent reduction, P = 0.0054. This was paralleled by a similar non-significant trend of between-haplotype difference in reduction of total cholesterol.

ConclusionThese preliminary pharmacogenetic results suggest that NPC1L1 variation is associated with inter-individual variation in response to ezetimibe treatment.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-511X-4-16 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Robert A Hegele - Justin Guy - Matthew R Ban - Jian Wang

Source: https://link.springer.com/



DOWNLOAD PDF




Related documents