Protein networks related to familial hypercholesterolemia gene

Alves, A.C.; Bourbon, M.

http://hdl.handle.net/10400.18/1632

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Authors

Alves, A.C.

Bourbon, M.

Abstract(s)

Familial hypercholesterolemia (FH) results mainly from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a lossof-function mutation in the LDLR receptor gene (LDLR) or mutations in the gene coding apolipoprotein B (APOB) or rare dominant gain-of-function mutations in a member of the pro-protein convertase family (PCSK9). However, mutations which encode a protein required for clathrin-mediated internalization of the LDLR (LDLRAP1) by the liver, have also been described as a recessive form of FH. The presence of mutations in other genes (CYP7A1, enzyme that catalyses the first step in the hepatic catabolism of cholesterol, and SREBP-2, a transcription factor that binds to the sterol regulatory element) have been described, but as very rare causes of hypercholesterolaemia. In the Portuguese FH Study, 60% of clinical FH patients do not present any mutation in the main 3 genes, indicating that the cause of hypercholesterolemia in these patients should be in another gene of lipid metabolism. The main aim of this project was the analysis of alterations found by exome sequencing of genes present in lipid metabolism protein/gene networks, namely LDLR, APOB, PCSK9 and LDLRAP1, in order to identify the genetic cause of the hypercholesterolemia in these patients.