LDL receptor function in Familial Hypercholesterolaemia
Research type
Research Study
Full title
A functional study to characterise LDL receptor activity in patients with familial hypercholesterolaemia using flow cytometry
IRAS ID
141898
Contact name
Anthony Wierzbicki
Contact email
Sponsor organisation
Guy's and St Thomas' Hospital
Research summary
Familial hypercholesterolaemia (FH) is an autosomal dominant condition caused by mutations in the low density lipoprotein receptor (LDLR) gene which accounts for majority of the cases seen, or the apolipoprotein B-100 (APOB) or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In patients with FH there is an increased level of total and low density lipoprotein cholesterol (LDL-C) in plasma which puts them at an increased risk of premature cardiovascular disease. Genetic analysis is used to identify known mutations in FH patients but there remains a group of these patients with FH phenotype but no genetic abnormality identified in the known genes screened. Assignation of the pathogenecity of the mutation is based on a variety of data sources including mutant receptors expressed in cell lines (gold standard) but more commonly is based on predictions from computer algorithms or from previously recorded families with high LDL-C and a family history of possible FH and early onset cardiovascular disease. A phenotypic assay would help resolve many questions about potential variants and clinically differentiate polygenic hypercholesterolaemia from those with monogenic FH. Various functional studies have been carried out to determine the activity of the LDLR in lymphocytes and demonstrate that a phenotypic LDLR activity assay may be feasible. The aim of this project is to evaluate LDLR activity in lymphocytes from FH patients using flow cytometry, and to determine if this technique may allow definitive assignment of genetic variants to pathological or normal groups.
REC name
London - Bromley Research Ethics Committee
REC reference
13/LO/1879
Date of REC Opinion
18 Dec 2013
REC opinion
Favourable Opinion