title: Genetic Architecture of Familial Hypercholesterolaemia.
abstract: Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation.
  
  
  
  Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology is most likely, due to the co-inheritance of common LDL-C-raising variants. The cardiovascular presentation and management of FH will differ between patients based on their underlying genetic factors. New genotyping methods such as next-generation sequencing will provide us with better understanding of the genetic architecture of FH.
authors.affiliation: Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK.|Department of Clinical Biochemistry, the Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK.
authors.forename: Mahtab
authors.initials: M
authors.lastname: Sharifi
authors.affiliation: Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Futema
authors.affiliation: Department of Clinical Biochemistry, the Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK.
authors.forename: Devaki
authors.initials: D
authors.lastname: Nair
authors.affiliation: Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK. steve.humphries@ucl.ac.uk.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D053299:Apolipoprotein B-100 / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D020412:Multifactorial Inheritance / Q000235:genetics; D009154:Mutation / Q000235:genetics; D000071449:Proprotein Convertase 9 / Q000097:blood / Q000235:genetics; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: APOB gene; Familial hypercholesterolaemia; LDLR gene; PCSK9 gene; Polygenic hypercholesterolaemia