© 1993 Oxford University Press
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The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variably-sized isoforms
Department of Biochemistry, Queen's University Kingston, Ontario K7L 3N6, Canada 1Department of Medicine and Surgery, University of Hamburg Martinistrasse 52, 2000 Hamburg 20, Germany 2Academic Medical Centre, University of Amsterdam, Centre for Thrombosis, Haemostasis and Inflammation Research Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
* To whom correspondence should be addressed
+ Present address: Academic Medical Centre, University of Amsterdam, Centre for Thrombosis, Haemostasis and Inflammation Research, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Elevated levels of plasma lipoprotein(a) [Lp(a)] have been correlated with the development of atherosclerosis in human populations. Apolipoprotein(a) [apo(a); the distinguishing protein component of Lp(a)] is characterized by multiple repeats of a sequence that closely resembles kringle IV of plasminogen. Variably-sized Lp(a) isoforms that are observed in the human population have been shown to occur as a result of differences in the numbers of the repeated kringle IV units in apo(a). Using PCR analysis of human liver mRNA, we have analyzed apo(a) from 10 unrelated individuals in order to determine the presence or absence of kringle IV repeat # 1, and #30–#37. Based on the apo(a) cDNA sequence published for one individual, these kringles all differ to some degree in amino acid sequence from the major kringle IV repeat, which is present in a number of identically repeated copies. We found that sequences corresponding to apo(a) kringle IV repeat #1, and #30– #37 were present in all individuals studied. This suggests that the inverse relationship that has been observed between Lp(a) isoform size and plasma Lp(a) levels is mediated by different numbers of identical kringle IV repeats, by an as yet undetermined mechanism. During the course of this study, we identified a Met
Thr polymorphism in the apo(a) kringle IV repeat #37. The calculated frequencies of the Met and Thr alleles were 0.58 and 0.42 respectively. We did not observe a correlation between the MetThr substitution and either plasma Lp(a) levels, or apo(a) transcript size.
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