The stromelysin-1 5A/6A promoter polymorphism is a disease marker for the extent of coronary heart disease.

Andreas Gardemann,Harald Tillmanns,Adelheid Schwarz,Werner Haberbosch

doi:10.1155/2002/418383

Abstract

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.

Highlights

Atherosclerosis is directly or indirectly related to nearly one half of all deaths in the Western world [1,2,3]
Total cholesterol, triglycerides, apolipoprotein AI (apoAI), apolipoprotein B (apoB), apoAI/apoB ratio, Lp(a), glucose, fibrinogen, prevalence of diabetes and arterial hypertension, body mass index (BMI) and cigarette consumption were almost identical between 5A/6A genotypes (i) of the total study population, (ii) of healthy controls, (iii) of patients without or with single- or multi-vessel disease and (iv) of subjects without and with myocardial infarction (MI)
Established risk factors for coronary artery disease (CAD) and MI were identified by multiple regression analysis or multiple logistic regression

Summary

Introduction

Atherosclerosis is directly or indirectly related to nearly one half of all deaths in the Western world [1,2,3]. Matrix metalloproteinases, such as stromelysin-1, are implicated in the pathogenesis of coronary artery disease (CAD) and acute myocardial infarction (MI). 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). 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

Methods

Results

Conclusion