A haplotype constituted of four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) is associated with coronary triple-vessel disease.
Vascular lesion development is associated with an accumulation of extracellular matrix proteins within the vessel wall. The proteins are degraded by matrix metalloproteinases (MMPs). There is also evidence indicating a participation of the MMPs in the weakening of atherosclerotic plaque that predisposes to lesion disruption. The aim of the study was to test an association among haplotypes of four single nucleotide MMP-2 promoter polymorphisms and the angiographically confirmed coronary triple-vessel disease (TVD). Incidence of haplotypes of four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) determined by PCR reactions with restriction analyses in 187 patients with coronary TVD (153 men, 34 women, age median 65 years) was compared to 196 control subjects without clinical signs of coronary heart disease (131 men and 65 women, age median 60 years). The incidence of two similar haplotypes was found to be different between patients and healthy subjects. The haplotype GCTC was more frequent in the TVD patients (P=0.01) though the haplotype GCGC was identified only in healthy subjects (P=0.001). Interestingly, the GCTC is the most frequent polymorphic haplotype composed of four promoter SNPs localized in the MMP-2 gene (53% in healthy subjects vs. 66% in patients with TVD) and the haplotype GCGC is the least frequent polymorphic one (4.4% in healthy subjects vs. 0% in patients with TVD). Two different MMP-2 promoter haplotypes differing only in -790T/G allele are significantly more or less frequent in coronary TVD compared to non-ischemic persons. Thus, the -790T/G MMP-2 genotype might be used as a genetic marker representing MMP-2 promoter variability for the TVD with odds ratio for TT and TG genotypes 2.59, 95% confidential interval 1.21-5.55, P=0.009. The analysis of promoter MMP-2 gene variability could help us to understand individual susceptibility to MMP inhibitor treatment of the coronary artery disease.
Vasků
Anna
A
Faculty of Medicine, Institute of Pathological Physiology, Masaryk University, Komenského nám. 2, 662 43 Brno, Czech Republic. avasku@med.muni.cz
Goldbergová
Monika
M
Izakovicová Hollá
Lydie
L
Sisková
Lenka
L
Groch
Ladislav
L
Beránek
Michal
M
Tschöplová
Svatava
S
Znojil
Vladimír
V
Vácha
Jirí
J
D000225:Adenine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013941:Thymine
D006147:Guanine; D003596:Cytosine; D020778:Matrix Metalloproteinase 2; D000225:Adenine; D013941:Thymine