Differential expression of double-band apolipoprotein(a) phenotypes in healthy Spanish subjects detected by SDS-agarose immunoblotting

A sodium dodecyl sulphate-agarose apolipoprotein(a) [apo(a)] phenotyping me thod was set up to attain accurate scanning densitometry of proteins. Serum samples from 99 healthy Spanish men were analysed and twenty-five differen t apo(a) isoforms (12 to 37 kringle 4 repeats) were detected. Double-band p henotypes accounted for 39.4% (n = 99) and three different patterns of prot ein expression were identified: pattern A (20.5% of double-band phenotyped samples) predominantly expressed the highest molecular weight isoform; patt ern B (53.9%) mainly the lowest molecular weight isoform, and pattern AB (2 5.6%), expressed both isoforms equally. A significant linear association be tween expression pattern and lipoprotein(a) [Lp(a)] concentration greater t han or equal to 0.30 g/l was observed. Single-band phenotyped samples (n = 60) were stratified according to apo(a) kringle 4 repeat categories and sho wed that 90% of isoforms < 20 K4 repeat!; had high Lp(a) concentrations (gr eater than or equal to 0.30 g/l), whereas isoforms with 20 to 24 or more th an 24 kringle 4 repeats had Lp(a) concentrations greater than or equal to 0 .30 g/l in 47% and 14%, respectively. A logistic regression model was fitte d to test the association between apo(a) size, expression pattern and Lp(a) concentration. In this model, apo(a) isoform < 25 kringle 4 repeats was si gnificantly associated with serum Lp(a) concentration greater than or equal to 0.30 g/l in both single and double-band phenotyped samples (odds ratio = 8.9, p < 0.001). In the latter, a differential expression pattern with re spect to smaller size isoforms (pattern AB vs A) was significantly associat ed with I;p(a) concentration greater than or equal to 0.30 g/l (odds ratio = 17.971 P = 0.045). Heterogeneity in protein apo(a) size expressed accordi ng to kringle 4 repeat number could be categorized in heterozygous phenotyp es as three patterns. When small-sized isoform was expressed (pattern B) or both isoforms were equally expressed (pattern AB), the probability of havi ng Lp(a) greater than or equal to 0.30 g/l is higher. (C) 1998 Elsevier Sci ence BN. All rights reserved.