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Journal of Lipid Research, Vol 31, 603-613, Copyright © 1990 by Lipid Research, Inc.
JW Gaubatz, KI Ghanem, J Guevara Jr, ML Nava, W Patsch and JD Morrisett
The plasma concentration of human lipoprotein[a], Lp[a], is highly
correlated with coronary artery disease. The protein moiety of Lp[a],
apoLp[a], consists of two apoproteins, apo[a] and apoB-100, linked by one
or more disulfide bonds(s). Apo[a], the protein unique to Lp[a], exists in
polymorphic forms that exhibit different apparent molecular weights (Mr).
Polyacrylamide gel electrophoresis in sodium dodecyl sulfate followed by
immunoblotting was used to separate and visualize these different forms and
to determine the polymorphic pattern of apo[a] in the plasma samples of 692
individuals. A total of 11 different polymorph bands ranging in Mr from 419
kD to 838 kD could be resolved, but only 1 or 2 bands were present per
individual. The polymorphic band pattern for an individual was assigned to
1 of the 66 different phenotype designations representing the total number
of possible single- and double-band combinations of the 11 detectable
bands. All 11 of the possible single-band phenotypes but only 32 of the 55
possible double-band phenotypes were represented. There were 412 plasma
samples (59.5%) that contained a single band, 274 (39.6%) contained two
bands, and only 6 (0.9%) had no detectable apo[a] band. A highly
significant inverse correlation was found between the Mr of the band(s)
present and the plasma apoLp[a] concentration (r = -0.461; rho = 0.0001).
The correlation was better between apoLp[a] and single-band (r = -0.495;
rho = 0.0001) than double-band (r = -0.382; rho = 0.0001) phenotypes. Of
the 274 individuals exhibiting double-band phenotypes, the lower Mr band
was more intense in 141 (51.4%), the two bands were equally intense in 85
(31.0%), while the higher Mr band was more intense in 48 (17.5%). Based
upon the hypothesis that apo[a] polymorphism is controlled by different
alleles at a single locus, the frequency of the 11 alleles determined from
the observe phenotypes (low Mr----high Mr) was: band 1) 419 kD, 0.00875;
band 2) 489 kD, 0.00510; band 3) 536 kD, 0.0555; band 4) 553 kD, 0.0758;
band 5) 613 kD, 0.135; band 6) 680 kD, 0.0824; band 7) 705 kD, 0.104; band
8) 742 kD, 0.151; band 9) 760 kD, 0.246; band 10) 796 kD, 0.128; band 11)
838 kD, 0.00802. The observed distribution of phenotypes in the population
was compared by chi-square analysis to that predicted on the basis of
simple Mendelian inheritance, and the hypothesis was rejected (chi 2 =
921.7; rho less than 0.001). Significantly, the singleband phenotypes are
over-represented in the population compared to that predicted.(ABSTRACT
TRUNCATED AT 400 WORDS)
ARTICLES
Polymorphic forms of human apolipoprotein[a]: inheritance and relationship of their molecular weights to plasma levels of lipoprotein[a]
Department of Medicine, Baylor College of Medicine, Houston, TX.
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