Impact of Aapo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect

Gaw, A., Brown, E. and Ford, I. (1998) Impact of Aapo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect. Arteriosclerosis, Thrombosis, and Vascular Biology, 18, pp. 1870-1876. (doi: 10.1161/01.ATV.18.12.1870)

Full text not currently available from Enlighten.

Abstract

Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of <20 kringle-4 (K-4) repeats, only 9% of the variability in Lp(a) concentration is explicable on the basis of the apo(a) length polymorphism. In those with apo(a) isoforms of >20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gaw, Dr Allan and Brown, Mrs Elizabeth and Ford, Professor Ian
Authors: Gaw, A., Brown, E., and Ford, I.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636

University Staff: Request a correction | Enlighten Editors: Update this record