Mechanisms of Low Levels of Apolipoprotein B

Cardiovascular Diseases Clinical Trial

Status Completed

Clinical Trial Summary

To determine mechanisms of low levels of apolipoprotein B.

Clinical Trial Description

BACKGROUND:

Elevated apoB levels are associated with an increased risk of coronary heart disease. Hypobetalipoproteinemia (HBLP) is characterized by apoB levels less than the 5 percentile. Dr. Welty, the principal investigator, sequenced mutations for truncated forms of apoB-67, apoB-55 and apoB-44.4 which causes HBLP, described a kindred from the Framingham Heart Study with HBLP due to an unidentified apoB gene mutation and purified apoB-67 containing lipoprotein particles. Heterozygous apoB-67 subjects have one normal allele making apoB-100; therefore, apoB levels would be predicted to be at least 50 percent of normal; however, they are 24 percent of normal. Dr. Welty has shown that these lower than expected levels result from decreased production of VLDL apoB-100, LDL apoB-100 and apoB-67, increased catabolism of VLDL apoB-100, and increased direct removal of apoB-67 from VLDL.

DESIGN NARRATIVE:

The first aim is to locate the apoB gene mutation in the Framingham kindred. The second aim is to perform stable isotope studies in the apoB-55 and apoB-44.4 kindreds to determine if apoB metabolism for these shorter truncations is similar to that for apoB-67. In aim three, apoB-100 synthesis is studied in heterozygous apoB-70 transgenic mice. If it is 25-25 percent of normal litter mates, the mechanism for this reduction in apoB-100 levels will be studied in hepatocytes isolated from the transgenic mice. In specific aim 4, size and composition of VLDL are compared in apoB-67 subjects and controls to determine if larger size or compositional changes account for the faster catabolism of VLDL apoB-100. The study has been extended through June 2007. ;

Study Design

N/A

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Heart Diseases
• Hypobetalipoproteinemia
• Hypobetalipoproteinemias

• NCT number: NCT00005565
• Study type: Observational
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Status: Completed
• Phase: N/A
• Start date: August 1997
• Completion date: June 2002