© 1995 Oxford University Press
RESEARCH-ARTICLE |
Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels
Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235 1Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA
*To whom correspondence should be addressed
Received May 5, 1995; Accepted June 23, 1995
Lipoprotein(a) [Lp(a)] is a cholesterol ester-rich atherogenic lipoprotein that is composed of a particle of low density lipoprotein and a large glycoprotein, apolipoprotein(a) [apo(a)]. Apolipoprotein(a) varies in size over a {small tilde}500 kDa range due to inter-allelic differences in the number of tandemly repeated kringle 4 (K4)-encoding 5. 5 kb sequences in the apo(a) gene. Only one of the 10 different types of K4 repeats in the apo(a) gene, the so-called type 2 K4 repeats, vary in number between apo(a) alleles. In this paper, we show that there is microheterogeneity within the sequence of the type 2 K4 repeat. Dralll restriction digestion and genomic blotting revealed that a subset of the type 2 K4-encoding sequences contained a Dralll site (K4-D). The proportion of apo(a) alleles that had at least one K4-D repeat ranged from 25% in Caucasians to 50% in the Chinese. K4-D repeats were clustered at the end(s) of the type 2 K4 tandem array and the number and patterns of the K4-D repeats were in linkage disequilibrium with flanking sequence polymorphisms; these features are remarkably similar to the minisatellite variant repeats (MVRs) found in variable number of tandem repeat sequences (VNTRs). In addition, a Dralll pattern that comprised 9% of the sample was invariably associated with low plasma levels of Lp(a) in Caucasians.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Rubin, H. J. Kim, T. A. Pearson, S. Holleran, R. Ramakrishnan, and L. Berglund Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a] J. Lipid Res., May 1, 2006; 47(5): 982 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ogorelkova, H. G. Kraft, C. Ehnholm, and G. Utermann Single nucleotide polymorphisms in exons of the apo(a) kringles IV types 6 to 10 domain affect Lp(a) plasma concentrations and have different patterns in Africans and Caucasians Hum. Mol. Genet., April 1, 2001; 10(8): 815 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. White, B. Guerra, J. Wang, and R. E. Lanford Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway J. Lipid Res., February 1, 1999; 40(2): 275 - 286. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Poon, X. Zhang, K. G. Dunsky, M. B. Taubman, and P. C. Harpel Apolipoprotein(a) Induces Monocyte Chemotactic Activity in Human Vascular Endothelial Cells Circulation, October 21, 1997; 96(8): 2514 - 2519. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. L. White, B. Guerra, and R. E. Lanford Influence of Allelic Variation on Apolipoprotein(a) Folding in the Endoplasmic Reticulum J. Biol. Chem., February 21, 1997; 272(8): 5048 - 5055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brunner, E.-M. Lobentanz, A. Petho-Schramm, A. Ernst, C. Kang, H. Dieplinger, H.-J. Muller, and G. Utermann The Number of Identical Kringle IV Repeats in Apolipoprotein(a) Affects Its Processing and Secretion by HepG2 Cells J. Biol. Chem., December 13, 1996; 271(50): 32403 - 32410. [Abstract] [Full Text] [PDF]
|
|