Familial hypercholesterolaemia (FH) is an inherited condition affecting at least one in 500, although current studies suggest that the frequency is much higher (1 in 250). Affected individuals are characterised by a significant increase of LDL cholesterol levels from birth. It is ussually caused by mutations in one of three genes (LDLR, APOB or PCSK9), however recently a polygenic cause of high LDL-C has been found to mimic the clinical FH phenotype. Our preliminary results showed that individuals with the polygenic form of FH have significantly higher triglyceride levels in comparison to the monogenic FH patients, which suggest that different metabolic pathways may be involved in the development of hypercholesterolaemia in these two forms of FH. We therefore would like to:

1) Compare the metabolomic profiles of the polygenic vs the monogenic FH to see if there are different pathways involved in the two groups

2) Focus on the known FH associated loci (LDLR and APOB) and compare the FH mutations versus common occuring polymorphisms in the same locus which have previously been associated with lipids in large scale association studies. This will help us test if the FH mutations are associated with metabolic changes different to those attributed to their genes in studies using healthy population samples.

Replication will be available through UCLEB where similar information is available.