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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1870-1876.)
© 1998 American Heart Association, Inc.

Original Contributions

Impact of Apo(a) Length Polymorphism and the Control of Plasma Lp(a) Concentrations

Evidence for a Threshold Effect

Allan Gaw; E. Ann Brown; Ian Ford; for the West of Scotland Coronary Prevention Study Group¹

From the Department of Pathological Biochemistry, Royal Infirmary (A.G., E.A.B.), and Robertson Centre for Biostatistics, University of Glasgow (I.F.), Glasgow, UK.

Correspondence to Dr A. Gaw, Department of Pathological Biochemistry, 4th Floor Queen Elizabeth Building, Royal Infirmary, University/NHS Trust, Glasgow G31 2ER, UK.

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.

Key Words: apolipoprotein(a) • lipoprotein(a) • polymorphism • phenotyping

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