Familial hyperlipidemia type 5 (WP5112)

Homo sapiens

Open in new tab Open in NDEx Open in Newt (SBGN)
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads
Familial hyperlipidemias are classified according to the Fredrickson classification. Type V familial hyperlipidemia is also known as combined hyperlipidemia as it look like a combination of type I and type IV. In type V familial hyperlipidemia there is an increase in both chylomicrons and VLDL. Both of the lipoproteins are hydrolyzed by LPL. However, this is mainly caused by mutations in APOA5. APOA5 plays a role in stablizing the APOC2-LPL complex, which is needed to hydrolize VLDL and chylomicrons. Mutations in APOA5 would therefore lead to instability of this complex and less hydrolysis. Some cases have also shown a decrease in LPL itself, which was mostly linked to the VLDL increase.

Authors

Ulas Babayigit and Eric Weitz

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Rare Diseases Serious Request 2024 - MetaKids

Annotations

Pathway Ontology

disease pathway

Disease Ontology

hyperlipoproteinemia type V familial hyperlipidemia

Cell Type Ontology

hepatocyte

Participants
Query Drugst.One

Label Type Compact URI Comment
Chylomicron Metabolite wikidata:Q423126
Chylomicron remnant Metabolite wikidata:Q14890553
VLDL Metabolite chebi:39027
Cholesterol Metabolite chebi:16113
HDL Metabolite chebi:47775
LDL Metabolite chebi:47774
Lipoprotein Metabolite chebi:6495
IDL Metabolite chebi:132933
Triglyceride Metabolite chebi:17855
Phospholipid Metabolite chebi:16247
SEL1L GeneProduct ensembl:ENSG00000071537
APOA2 GeneProduct ensembl:ENSG00000158874
LRP1 GeneProduct ensembl:ENSG00000123384
APOA4 GeneProduct ensembl:ENSG00000110244
CETP GeneProduct ensembl:ENSG00000087237
LIPC GeneProduct ensembl:ENSG00000166035
APOA1 GeneProduct ensembl:ENSG00000118137
LCAT GeneProduct ensembl:ENSG00000213398
LDLR GeneProduct ensembl:ENSG00000130164
PLTP GeneProduct ensembl:ENSG00000100979
LPL GeneProduct ensembl:ENSG00000175445
LMF1 GeneProduct ensembl:ENSG00000103227
GPIHBP1 GeneProduct ensembl:ENSG00000277494
APOC2 GeneProduct ensembl:ENSG00000234906
APOA5 GeneProduct ensembl:ENSG00000110243

References

  1. Two cases with transient lipoprotein lipase (LPL) activity impairment: evidence for the possible involvement of an LPL inhibitor. Nagasaka H, Kikuta H, Chiba H, Murano T, Harashima H, Ohtake A, et al. Eur J Pediatr. 2003 Mar;162(3):132–8. PubMed Europe PMC Scholia
  2. Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Go GW, Mani A. Yale J Biol Med. 2012 Mar;85(1):19–28. PubMed Europe PMC Scholia
  3. Cholesteryl ester transfer protein inhibitors for dyslipidemia: focus on dalcetrapib. Goldberg AS, Hegele RA. Drug Des Devel Ther. 2012;6:251–9. PubMed Europe PMC Scholia
  4. Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study. Todur SP, Ashavaid TF. Indian J Clin Biochem. 2013 Apr;28(2):116–23. PubMed Europe PMC Scholia
  5. Introduction to Lipids and Lipoproteins. Feingold KR. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2021. PubMed Europe PMC Scholia
  6. High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol. Tosheska Trajkovska K, Topuzovska S. Anatol J Cardiol. 2017 Aug;18(2):149–54. PubMed Europe PMC Scholia
  7. Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism. Wolska A, Dunbar RL, Freeman LA, Ueda M, Amar MJ, Sviridov DO, et al. Atherosclerosis. 2017 Dec;267:49–60. PubMed Europe PMC Scholia
  8. N-terminal mutation of apoA-I and interaction with ABCA1 reveal mechanisms of nascent HDL biogenesis. Liu M, Mei X, Herscovitz H, Atkinson D. J Lipid Res. 2019 Jan;60(1):44–57. PubMed Europe PMC Scholia
  9. Genetic and secondary causes of severe HDL deficiency and cardiovascular disease. Geller AS, Polisecki EY, Diffenderfer MR, Asztalos BF, Karathanasis SK, Hegele RA, et al. J Lipid Res. 2018 Dec;59(12):2421–35. PubMed Europe PMC Scholia
  10. Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice. Obinata H, Kuo A, Wada Y, Swendeman S, Liu CH, Blaho VA, et al. J Lipid Res. 2019 Nov;60(11):1912–21. PubMed Europe PMC Scholia
  11. Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis. Lucero D, Islam P, Freeman LA, Jin X, Pryor M, Tang J, et al. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Feb;1865(2):158537. PubMed Europe PMC Scholia
  12. Association between the APOA2 rs3813627 Single Nucleotide Polymorphism and HDL and APOA1 Levels Through BMI. Boughanem H, Bandera-Merchán B, Hernández-Alonso P, Moreno-Morales N, Tinahones FJ, Lozano J, et al. Biomedicines. 2020 Feb 27;8(3):44. PubMed Europe PMC Scholia
  13. Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease. Chait A, Ginsberg HN, Vaisar T, Heinecke JW, Goldberg IJ, Bornfeldt KE. Diabetes. 2020 Apr;69(4):508–16. PubMed Europe PMC Scholia