KEGG DISEASE: Familial hypercholesterolemia

DISEASE: Familial hypercholesterolemia

Entry

H00155                      Disease

Name

Familial hypercholesterolemia;
Autosomal dominant hypercholesterolaemia

Subgroup

Familial autosomal recessive hypercholesterolemia [DS:H01918]

Supergrp

Hyperlipidemia [DS:H01635]

Description

Familial hypercholesterolaemia (FHCL) is an autosomal dominant disorder caused by deficiency of low density lipoprotein receptor. Other forms of this disorder include hypercholesterolemia caused by mutation of APOB or PCSK9 gene. This disorder is characterized by severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. Patients have a significantly elevated risk of early coronary heart disease.

Category

Inherited metabolic disorder

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Disorders of lipoprotein metabolism or certain specified lipidaemias
    5C80  Hyperlipoproteinaemia
     H00155  Familial hypercholesterolemia
Pathway-based classification of diseases [BR:br08402]
Endocrine system
  nt06320  APOB-LDLR signaling
   H00155  Familial hypercholesterolemia

Pathway

hsa04979

Cholesterol metabolism

hsa04975

Fat digestion and absorption

Network

nt06320 APOB-LDLR signaling

Gene

(FHCL1) LDLR [HSA:3949] [KO:K12473]
(FHCL1) EPHX2 [HSA:2053] [KO:K08726]
(FHCL1) GHR [HSA:2690] [KO:K05080]
(FHCL1) PPP1R17 [HSA:10842] [KO:K08067]
(FHCL1) APOA2 [HSA:336] [KO:K08758]
(FHCL2) APOB [HSA:338] [KO:K14462]
(FHCL3) PCSK9 [HSA:255738] [KO:K13050]
(FHCL4) LDLRAP1 [HSA:26119] [KO:K12474]

Drug

Simvastatin [DR:D00434]
Pravastatin sodium [DR:D00893]
Fluvastatin sodium [DR:D00892] (Heterozygous familial)
Atorvastatin calcium [DR:D02258]
Rosuvastatin calcium [DR:D01915]
Ezetimibe [DR:D01966]
Mipomersen sodium [DR:D08946]
Lomitapide mesylate [DR:D09638]
Evolocumab [DR:D10557]
Alirocumab [DR:D10335]
Bempedoic acid [DR:D10691]
Inclisiran [DR:D11931]
Inclisiran sodium [DR:D12293]
Evinacumab [DR:D11753]
Niacin and lovastatin [DR:D10292]
Ezetimibe and simvastatin [DR:D10257]
Bempedoic acid and ezetimibe [DR:D11794]
Ezetimibe and rosuvastatin [DR:D11520]

Other DBs

ICD-11:

5C80.00

ICD-10:

E78.0

MeSH:

D006937

OMIM:

143890 144010 603776 603813

Reference

PMID:18607183

Authors

Humphries SE, Norbury G, Leigh S, Hadfield SG, Nair D

Title

What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?

Journal

Curr Opin Lipidol 19:362-8 (2008)
DOI:10.1097/MOL.0b013e32830636e5

Reference

PMID:15657617

Authors

Newson AJ, Humphries SE

Title

Cascade testing in familial hypercholesterolaemia: how should family members be contacted?

Journal

Eur J Hum Genet 13:401-8 (2005)
DOI:10.1038/sj.ejhg.5201360

Reference

PMID:15990592

Authors

Hadfield SG, Humphries SE

Title

Implementation of cascade testing for the detection of familial hypercholesterolaemia.

Journal

Curr Opin Lipidol 16:428-33 (2005)
DOI:10.1097/01.mol.0000174152.76554.d6

Reference

PMID:11389828 (LDLR)

Authors

Koivisto UM, Hubbard AL, Mellman I

Title

A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor.

Journal

Cell 105:575-85 (2001)
DOI:10.1016/s0092-8674(01)00371-3

Reference

PMID:14673705 (EPHX2)

Authors

Sato K, Emi M, Ezura Y, Fujita Y, Takada D, Ishigami T, Umemura S, Xin Y, Wu LL, Larrinaga-Shum S, Stephenson SH, Hunt SC, Hopkins PN

Title

Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred.

Journal

J Hum Genet 49:29-34 (2004)
DOI:10.1007/s10038-003-0103-6

Reference

PMID:12910492 (GHR)

Authors

Takada D, Ezura Y, Ono S, Iino Y, Katayama Y, Xin Y, Wu LL, Larringa-Shum S, Stephenson SH, Hunt SC, Hopkins PN, Emi M

Title

Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred.

Journal

Am J Med Genet A 121A:136-40 (2003)
DOI:10.1002/ajmg.a.20172

Reference

PMID:12955585 (PPP1R17)

Authors

Ono S, Ezura Y, Emi M, Fujita Y, Takada D, Sato K, Ishigami T, Umemura S, Takahashi K, Kamimura K, Bujo H, Saito Y

Title

A promoter SNP (-1323T>C) in G-substrate gene (GSBS) correlates with hypercholesterolemia.

Journal

J Hum Genet 48:447-450 (2003)
DOI:10.1007/s10038-003-0055-x

Reference

PMID:12522687 (APOA2)

Authors

Takada D, Emi M, Ezura Y, Nobe Y, Kawamura K, Iino Y, Katayama Y, Xin Y, Wu LL, Larringa-Shum S, Stephenson SH, Hunt SC, Hopkins PN

Title

Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred.

Journal

J Hum Genet 47:656-64 (2002)
DOI:10.1007/s100380200101

Reference

PMID:10952765 (APOB)

Authors

Saint-Jore B, Varret M, Dachet C, Rabes JP, Devillers M, Erlich D, Blanchard P, Krempf M, Mathe D, Chanu B, Jacotot B, Farnier M, Bonaiti-Pellie C, Junien C, Boileau C

Title

Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective contributions of LDLR and APOB gene defects as well as a third major group of defects.

Journal

Eur J Hum Genet 8:621-30 (2000)
DOI:10.1038/sj.ejhg.5200516

Reference

PMID:12730697 (PCSK9)

Authors

Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C

Title

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Journal

Nat Genet 34:154-6 (2003)
DOI:10.1038/ng1161

Reference

PMID:12016260 (LDLRAP1)

Authors

Al-Kateb H, Bahring S, Hoffmann K, Strauch K, Busjahn A, Nurnberg G, Jouma M, Bautz EK, Dresel HA, Luft FC

Title

Mutation in the ARH gene and a chromosome 13q locus influence cholesterol levels in a new form of digenic-recessive familial hypercholesterolemia.

Journal

Circ Res 90:951-8 (2002)
DOI:10.1161/01.res.0000018002.43041.08

LinkDB

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