The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease

Background. Matrix metalloproteinases, such as stromelysin-1, are implicated in the pathogenesis of coronary artery disease (CAD) and acute myocardial infarction (MI). A 5A/6A promoter polymorphism can regulate the transcription of the stromelysin-1 gene in an allele-specific manner. Evidence has be...

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Autores principales: Schwarz, Adelheid, Haberbosch, Werner, Tillmanns, Harald, Gardemann, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851962/
https://www.ncbi.nlm.nih.gov/pubmed/12515907
http://dx.doi.org/10.1155/2002/418383
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author Schwarz, Adelheid
Haberbosch, Werner
Tillmanns, Harald
Gardemann, Andreas
author_facet Schwarz, Adelheid
Haberbosch, Werner
Tillmanns, Harald
Gardemann, Andreas
author_sort Schwarz, Adelheid
collection PubMed
description Background. Matrix metalloproteinases, such as stromelysin-1, are implicated in the pathogenesis of coronary artery disease (CAD) and acute myocardial infarction (MI). A 5A/6A promoter polymorphism can regulate the transcription of the stromelysin-1 gene in an allele-specific manner. Evidence has been presented that the 6A allele is associated with the progression of coronary heart disease (CHD). In contrast, the 5A allele may be linked to the risk of MI. Results. To analyse the relation of the 5A/6A polymorphism with the risk and severity of CHD and the risk of MI, a case-control study of 515 healthy controls and 1848 participants who underwent coronary angiography for diagnostic purposes was conducted. In the total sample, the mean CHD scores—according to Gensini—were different between 5A/6A genotypes: 5A5A homozygotes had the lowest, 6A6A genotypes the highest and 5A6A heterozygotes intermediate scores. These differences were even more pronounced when the participants were restricted to individuals with a high coronary risk profile (high apoB levels, high Lp(a) levels, high glucose levels, combinations of either high apoB and Lp(a) levels or high apoB, Lp(a) and glucose plasma levels). Mean values were used as cut points for high-risk populations, respectively. In contrast, the 5A allele was not associated with the risk of CHD or MI. Even when angiographically controlled individuals without MI were compared with MI patients in subpopulations of participants with no, single, double and triple vessel disease, the frequencies of the 5A/6A and/or the 5A5A genotypes were not higher in each subgroup, respectively. Conclusions. The present results do not confirm an association of the 5A allele with the risk of MI, observed in another investigation, but strengthen the hypothesis of earlier studies that the 6A allele is a disease marker for progression of coronary heart disease. Further investigations should evaluate whether 6A allele carriers and especially 6A homozygotes might benefit from a more aggressive therapy against CHD progression.
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spelling pubmed-38519622013-12-25 The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease Schwarz, Adelheid Haberbosch, Werner Tillmanns, Harald Gardemann, Andreas Dis Markers Other Background. Matrix metalloproteinases, such as stromelysin-1, are implicated in the pathogenesis of coronary artery disease (CAD) and acute myocardial infarction (MI). A 5A/6A promoter polymorphism can regulate the transcription of the stromelysin-1 gene in an allele-specific manner. Evidence has been presented that the 6A allele is associated with the progression of coronary heart disease (CHD). In contrast, the 5A allele may be linked to the risk of MI. Results. To analyse the relation of the 5A/6A polymorphism with the risk and severity of CHD and the risk of MI, a case-control study of 515 healthy controls and 1848 participants who underwent coronary angiography for diagnostic purposes was conducted. In the total sample, the mean CHD scores—according to Gensini—were different between 5A/6A genotypes: 5A5A homozygotes had the lowest, 6A6A genotypes the highest and 5A6A heterozygotes intermediate scores. These differences were even more pronounced when the participants were restricted to individuals with a high coronary risk profile (high apoB levels, high Lp(a) levels, high glucose levels, combinations of either high apoB and Lp(a) levels or high apoB, Lp(a) and glucose plasma levels). Mean values were used as cut points for high-risk populations, respectively. In contrast, the 5A allele was not associated with the risk of CHD or MI. Even when angiographically controlled individuals without MI were compared with MI patients in subpopulations of participants with no, single, double and triple vessel disease, the frequencies of the 5A/6A and/or the 5A5A genotypes were not higher in each subgroup, respectively. Conclusions. The present results do not confirm an association of the 5A allele with the risk of MI, observed in another investigation, but strengthen the hypothesis of earlier studies that the 6A allele is a disease marker for progression of coronary heart disease. Further investigations should evaluate whether 6A allele carriers and especially 6A homozygotes might benefit from a more aggressive therapy against CHD progression. IOS Press 2002 2002-12-04 /pmc/articles/PMC3851962/ /pubmed/12515907 http://dx.doi.org/10.1155/2002/418383 Text en Copyright © 2002 Hindawi Publishing Corporation.
spellingShingle Other
Schwarz, Adelheid
Haberbosch, Werner
Tillmanns, Harald
Gardemann, Andreas
The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title_full The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title_fullStr The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title_full_unstemmed The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title_short The Stromelysin-1 5A/6A Promoter Polymorphism Is a Disease Marker for the Extent of Coronary Heart Disease
title_sort stromelysin-1 5a/6a promoter polymorphism is a disease marker for the extent of coronary heart disease
topic Other
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851962/
https://www.ncbi.nlm.nih.gov/pubmed/12515907
http://dx.doi.org/10.1155/2002/418383
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