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.
