Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence.
OBJECTIVE
Matrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.


METHODS
Study enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms -1607 1G/2G, -519 A/G and -340 T/C were genotyped by PCR and RFLP methods.


RESULTS
Individuals carrying MMP-1 -1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR=1; OR=1.87 95% CI 1.29-2.07; OR=3.49 95% CI 1.67-7.30, p=0.0009, respectively). Compared to the referent haplotype 2G(-1607)-T(-340)-A(-519), the haplotypes 1G(-1607)-T(-340)-A(-519), 1G(-1607)-T(-340)-G(-519) and 2G(-1607)-C(-340)-A(-519) had statistically significant protective effect on CP presence (OR=0.41, 95% CI 0.29-0.81, p=0.01; OR=0.56, 95% CI 0.44-0.89, p=0.01; OR=0.43, 95% CI 0.27-0.86, p=0.02, respectively).


CONCLUSIONS
MMP-1 -1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.
VINČA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia. tamariska@vinca.rs
Tamara
T
Djurić
Ljiljana
L
Stojković
Maja
M
Zivković
Igor
I
Končar
Aleksandra
A
Stanković
Ana
A
Djordjević
Dragan
D
Alavantić
D000328:Adult; D000368:Aged; D054458:Amplified Fragment Length Polymorphism Analysis; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA
C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1