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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1997-8-18
|
| pubmed:abstractText |
Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant independent risk factor for the development of atherosclerosis. Interindividual levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for sequence polymorphisms in the K.IV coding domain, we identified a polymorphism predicting a Thr-->Pro substitution located at amino acid position 12 of kringle IV type 8 of apo(a). The functional and clinical significance of this polymorphism was analysed in a case-control study and by comparing the in vitro lysine binding characteristics of the two Lp(a) subtypes. The case-control study (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender matched normolipidemic controls) revealed a overall allele frequency for the Thr12-->Pro substitution in kringle IV type 8 of 14% and a negative association between presence of the Pro12-subtype and symptomatic atherosclerosis (p < 0.03). The in vitro lysine binding studies, using Lp(a) isolated from subjects homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine-Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for immobilised plasmin degraded des-AA-fibrin (Desafib-X) was also comparable for the two subtypes, however a decreased maximal attainable binding (Bmax) for immobilised desafib-X was observed for the Pro12-subtype Lp(a).
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoprotein(a),
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0340-6245
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
77
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
949-54
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9184408-Adult,
pubmed-meshheading:9184408-Arteriosclerosis,
pubmed-meshheading:9184408-Case-Control Studies,
pubmed-meshheading:9184408-DNA Primers,
pubmed-meshheading:9184408-Female,
pubmed-meshheading:9184408-Humans,
pubmed-meshheading:9184408-Kringles,
pubmed-meshheading:9184408-Lipoprotein(a),
pubmed-meshheading:9184408-Male,
pubmed-meshheading:9184408-Phenotype,
pubmed-meshheading:9184408-Plasminogen,
pubmed-meshheading:9184408-Polymerase Chain Reaction,
pubmed-meshheading:9184408-Polymorphism, Genetic,
pubmed-meshheading:9184408-Proline,
pubmed-meshheading:9184408-Protein Structure, Secondary,
pubmed-meshheading:9184408-Reference Values,
pubmed-meshheading:9184408-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:9184408-Risk Factors,
pubmed-meshheading:9184408-Sequence Homology, Nucleic Acid,
pubmed-meshheading:9184408-Threonine
|
| pubmed:year |
1997
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| pubmed:articleTitle |
The identification and significance of a Thr-->Pro polymorphism in kringle IV type 8 of apolipoprotein(a).
|
| pubmed:affiliation |
Department of Clinical Chemistry, University Hospital Utrecht, The Netherlands. j.prins@lab.azu.nl
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| pubmed:publicationType |
Journal Article
|