Skip Navigation LinksHome > June 2014 - Volume 25 - Issue 3 > Familial combined hyperlipidemia: from molecular insights to...
Current Opinion in Lipidology:
doi: 10.1097/MOL.0000000000000068
LIPID METABOLISM: Edited by Ernst J. Schaefer

Familial combined hyperlipidemia: from molecular insights to tailored therapy

van Greevenbroek, Marleen M.J.a,b; Stalenhoef, Anton F.H.c; de Graaf, Jacquelinec; Brouwers, Martijn C.G.J.a

Collapse Box

Abstract

Purpose of review

This review presents recent basic and clinical developments in familial combined hyperlipidemia (FCHL).

Recent findings

A variety of experiments have contributed to the elucidation of this complex disease. They consist of dynamic and gene expression studies in adipocytes, confirming the role of dysfunctional adipose tissue in the pathogenesis of FCHL and identifying potential new pathways, such as complement activation. Whole exome sequencing and classical linkage studies in FCHL pedigrees, some conducted with new traits (e.g. plasma proprotein convertase subtilisin/kexin type 9 [PCSK9] and phospholipid transfer protein activity), have revealed new genes of interest, among which SLC25A40 and LASS4. Finally, gene expression studies in liver biopsies and liver cell culture experiments have gained further insight in the role of upstream stimulatory factor 1, one of the most replicated genes in FCHL, in its pathogenesis.

On the basis of these observations and recent phase II clinical trials, PCSK9 antagonizing is the most promising lipid-lowering therapy to be added to our current arsenal of statins and fibrates in FCHL treatment.

Summary

Ongoing basic research provides a steady growth in our knowledge on the genes that are involved in FCHL as well as their metabolic function(s). This field of research may be enhanced when data are expanded and integrated for systems biology approaches. Our growing insights in the cause of FCHL allow for better, targeted treatment of dyslipidemia and prevention of cardiovascular complications.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.