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

被引：89

作者：

Hegele R.A. ^{[1
,2
]}

Guy J. ^{[1
]}

Ban M.R. ^{[1
]}

Wang J. ^{[1
]}

机构：

[1] Vascular Biology Group, Robarts Research Institute, London, Ont.

[2] Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.

来源：

Lipids in Health and Disease | / 4卷 / 1期

关键词：

Rosuvastatin; Ezetimibe; Pairwise Linkage Disequilibrium; Shrimp Alkaline Phosphatase; Ezetimibe Treatment;

D O I：

10.1186/1476-511X-4-16

中图分类号：

学科分类号：

摘要：

Background: NPC1L1 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. Results: In 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. Conclusion: These preliminary pharmacogenetic results suggest that NPC1L1 variation is associated with inter-individual variation in response to ezetimibe treatment. © 2005 Hegele et al; licensee BioMed Central Ltd.

引用

共 15 条

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