Sequence polymorphisms in the apo(a) gene associated with specific levels of Lp(a) in plasma.

Details

Serval ID
serval:BIB_9E565B89B4D5
Type
Article: article from journal or magazin.
Collection
Publications
Title
Sequence polymorphisms in the apo(a) gene associated with specific levels of Lp(a) in plasma.
Journal
Human Molecular Genetics
Author(s)
Mooser V., Mancini F.P., Bopp S., Pethö-Schramm A., Guerra R., Boerwinkle E., Müller H.J., Hobbs H.H.
ISSN
0964-6906 (Print)
ISSN-L
0964-6906
Publication state
Published
Issued date
1995
Volume
4
Number
2
Pages
173-181
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't,
Abstract
Most of the interindividual variations in plasma levels of lipoprotein(a) [Lp(a)] can be attributed to sequence differences linked to the apolipoprotein(a) [apo(a)] locus. Plasma levels of Lp(a) tend to be inversely related to the number of kringle 4 (K4)-encoding sequences in the apo(a) gene, but there are several exceptions to this general trend. Other aspects of the apo(a) gene, in addition to the number of K4 repeats, affect plasma levels of Lp(a). To identify sequences in the apo(a) gene that contribute to plasma Lp(a) levels, we characterized the relationship between a length polymorphism [(TTTTA)n] located 1.3 kb 5' of the first exon of the apo(a) gene, the number of K4 repeats in the gene, and the plasma levels of Lp(a). There was significant linkage disequilibrium between the number of TTTTA repeats and the number of K4 repeats. All of the apo(a) alleles with 11 TTTTA repeats contained fewer than 24 K4 repeats and were paradoxically associated with low plasma Lp(a) levels (< or = mg/dl). To determine whether this association was due to the effect of the 11 TTTTA copies on apo(a) gene transcription, we measured the ability of fragments containing 11 or eight TTTTA repeats to promote transcription when introduced into cultured human hepatocarcinoma cells. No difference was found in the transcriptional activity of the two fragments. The TTTTA repeat constitutes the first sequence polymorphism at the apo(a) locus, other than the number of K4 repeats, which is associated with plasma concentrations of Lp(a).
Keywords
African Continental Ancestry Group/genetics, Alleles, Apolipoproteins A/genetics, Asian Continental Ancestry Group/genetics, Base Sequence, DNA, European Continental Ancestry Group/genetics, Exons, Family Health, Genes, Reporter, Genome, Human, Humans, Introns, Lipoprotein(a)/blood, Lipoprotein(a)/genetics, Luciferases/genetics, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Genetic/genetics, Polymorphism, Restriction Fragment Length, Polymorphism, Single-Stranded Conformational, Repetitive Sequences, Nucleic Acid/genetics, Transcription, Genetic
Pubmed
Web of science
Create date
13/10/2013 21:07
Last modification date
20/08/2019 15:04
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