Mechanisms of Low Levels of Apolipoprotein B

Cardiovascular Diseases Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005565
• Other study ID #: 5114
• Secondary ID: R01HL056895
• Status: Completed
• Phase: N/A
• First received: May 25, 2000
• Last updated: July 28, 2016
• Start date: August 1997
• Est. completion date: June 2002

Study information

• Verified date: January 2008
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

To determine mechanisms of low levels of apolipoprotein B.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2002
• Est. primary completion date: June 2002
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 100 Years
• Eligibility: No eligibility criteria

Study Design

N/A

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Heart Diseases
• Hypobetalipoproteinemia
• Hypobetalipoproteinemias

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (5)

Matthan NR, Welty FK, Barrett PH, Harausz C, Dolnikowski GG, Parks JS, Eckel RH, Schaefer EJ, Lichtenstein AH. Dietary hydrogenated fat increases high-density lipoprotein apoA-I catabolism and decreases low-density lipoprotein apoB-100 catabolism in hypercholesterolemic women. Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1092-7. Epub 2004 Apr 15. — View Citation

Welty FK, Guida KA, Andersen JJ. Donor splice-site mutation (210+1G_C) in the ApoB gene causes a very low level of ApoB-100 and LDL cholesterol. Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1864-5. — View Citation

Welty FK, Lichtenstein AH, Barrett PH, Dolnikowski GG, Schaefer EJ. Human apolipoprotein (Apo) B-48 and ApoB-100 kinetics with stable isotopes. Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2966-74. — View Citation

Welty FK, Lichtenstein AH, Barrett PH, Dolnikowski GG, Schaefer EJ. Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes. Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1703-7. Epub 2004 Jul 8. — View Citation

Welty FK, Lichtenstein AH, Barrett PH, Jenner JL, Dolnikowski GG, Schaefer EJ. Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans. Arterioscler Thromb Vasc Biol. 2000 Jul;20(7):1807-10. — View Citation