Subclasses of low-density lipoprotein and very low-density lipoprotein in familial combined hyperlipidemia: relationship to multiple lipoprotein phenotype.

Abstract

OBJECTIVE:

The present study addresses the presence of distinct metabolic phenotypes in familial combined hyperlipidemia (FCHL) in relation to small dense low-density lipoprotein (sd LDL) and very low-density lipoprotein (VLDL) subclasses.

METHODS AND RESULTS:

Hyperlipidemic FCHL relatives (n=72) were analyzed for LDL size by gradient gel electrophoresis. Pattern B LDL (sd LDL, particle size <258 A) and pattern A LDL (buoyant LDL, particle size > or =258 A) were defined. Analyses showed bimodal distribution of LDL size associated with distinct phenotypes. Subjects with predominantly large, buoyant LDL showed a hypercholesterolemic phenotype and the highest apo B levels. Subjects with predominantly sd LDL showed a hypertriglyceridemic, low high-density lipoprotein (HDL) cholesterol phenotype, with moderately elevated apoB, total cholesterol level, and LDL cholesterol level. Subjects with both buoyant LDL and sd LDL (pattern AB, n=7) showed an intermediate phenotype, with high normal plasma triglycerides. VLDL subfraction analysis showed that the sd LDL phenotype was associated with a 10-times higher number of VLDL1 particles of relatively lower apo AI and apo E content, as well as smaller VLDL2 particles, in combination with increased plasma insulin concentration in comparison to pattern A.

CONCLUSIONS:

The present observations underscore the importance of the VLDL triglyceride metabolic pathway in FCHL as an important determinant of the phenotypic heterogeneity of the disorder.

• Authors: A M Georgieva, M M J van Greevenbroek, R M Krauss, M C G J Brouwers, V M M-J Vermeulen, M G Robertus-Teunissen, C J H van der Kallen, T W A de Bruin
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 4 Pg. 744-9 (Apr 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 14751815 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoprotein A-I
• Apolipoproteins E
• Insulin
• Lipoproteins, LDL
• Lipoproteins, VLDL

Topics

• Adult
• Apolipoprotein A-I (blood)
• Apolipoproteins E (blood)
• Blood Protein Electrophoresis
• Female
• Humans
• Hypercholesterolemia (blood, genetics)
• Hyperlipidemia, Familial Combined (blood, genetics)
• Hyperlipoproteinemia Type IV (blood, genetics)
• Insulin (blood)
• Lipoproteins, LDL (blood, classification)
• Lipoproteins, VLDL (blood, classification)
• Male
• Particle Size
• Phenotype