Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe.

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Wang J, Williams CM, Hegele RA

Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe.

Clin Genet. 2005 Feb;67(2):175-7.

PubMed ID

15679830 [ View in PubMed

]

Abstract

Ezetimibe reduces plasma low-density lipoprotein (LDL) cholesterol by blocking sterol absorption in enterocytes. The NPC1L1 gene product was recently identified as the molecular target for ezetimibe, although functional details are incomplete. We used the non-response phenotype of plasma LDL cholesterol to ezetimibe treatment to ascertain individuals who might have variant NPC1L1. We found that one non-responder to ezetimibe was a compound heterozygote for two rare non-synonymous polymorphisms in NPC1L1 that were absent in normal control subjects. We also characterized other NPC1L1 polymorphisms. While there are many explanations for non-response to medications, our data suggest a possible relationship between NPC1L1 variation and ezetimibe response and further indicate that a non-response phenotype might ascertain subjects with genomic DNA variants that could help define metabolic pathways.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ezetimibe	Niemann-Pick C1-like protein 1	Protein	Humans	Yes	Inhibitor	Details

Polypeptides

Name	UniProt ID
Niemann-Pick C1-like protein 1	Q9UHC9	Details

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Ezetimibe	Approved	LDL cholesterol	decreased	Ezetimibe decreases the level of LDL cholesterol in the blood