Protective effects of angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A polymorphisms on dilatative pathology within the ascending thoracic aorta.
OBJECTIVE
Activation of matrix metalloproteinases and the renin/angiotensin signaling pathways is under investigation with regard to their potential pathogenesis in dilatative pathology of the aorta. The purpose of this study was to explore matrix metalloproteinase-3 5A/6A and angiotensin-converting enzyme I/D polymorphisms as predisposing factors to dilatative pathology of the aorta.


METHODS
We studied 107 patients who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n = 773), all from Lithuania. The insertion/deletion (-1171 5A/6A) polymorphism in the promoter region of matrix metalloproteinase-3 studied by real-time polymerase-chain-reaction amplification and the D and I alleles were identified on the basis of standard polymerase-chain-reaction amplification of the respective fragments from intron 16 of the angiotensin-converting enzyme gene.


RESULTS
The frequency of the angiotensin-converting enzyme D allele was significantly higher in dilatative pathology of ascending thoracic aorta patients than in the reference group subjects (0.55 vs 0.48, respectively). The latter group had a significantly higher frequency of the angiotensin-converting enzyme I/I genotype than in dilatative pathology of ascending thoracic aorta patients (27.4% vs 16.5%, respectively). In the reference group, the frequency of combined angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A genotypes was 7.5%, while in the dilatative pathology of ascending thoracic aorta patient group, there was no one carrying that combined genotype (p = 0.001).


CONCLUSIONS
The present study showing a role of angiotensin-converting enzyme and matrix metalloproteinase-3 in the development of dilatative pathology of ascending thoracic aorta permits us to entertain a possible protective mechanism for the combined effects of the angiotensin-converting enzyme I/I and the matrix metalloproteinase-3 6A/6A genotypes.
Laboratory of Molecular Cardiology, Institute of Cardiology, Kaunas University of Medicine, Kaunas, Lithuania. vaiva.lesauskaite@med.kmu.lt
Vaiva
V
Lesauskaite
Giedre
G
Sinkunaite-Marsalkiene
Abdonas
A
Tamosiunas
Rimantas
R
Benetis
D000368:Aged; D000784:Aortic Dissection / Q000201:enzymology / Q000235:genetics / Q000601:surgery; D017545:Aortic Aneurysm, Thoracic / Q000201:enzymology / Q000235:genetics* / Q000601:surgery; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D019278:Matrix Metalloproteinase 3