Phenotypes of myocardial blood perfusion related to the genetic variations of metalloproteinases 3 (MMP3) and 9 (MMP9)

The myocardial perfusion is modified more frequently by coronary atherosclerosis, which can lead to cardiac dysfunction. The allelic variants can induce different phenotypes of left ventricle remodelling. The factors for expression of phenotypes of myocardial blood perfusion are not completely understood. The purpose of this study was to evaluate the influence of single nucleotide polymorphisms of metalloproteinase 3 (MMP3; rs3025058) and metalloproteinase 9 (MMP9; rs3918242) genes in the myocardial blood perfusion, and to determine the allelic variants that influence the susceptibility of myocardial perfusion abnormalities. Two hundred and five patients underwent myocardial perfusion imaging (MPI) with 99mTc-tetrofosmin in which was carried out for genotyping of MMP3 and MMP9 promoter gene polymorphism. Negative MPI to myocardial ischaemia was defined by absent of myocardial perfusion defects (MPD) and positive MPI to myocardial ischaemia was defined by presence of one or more reversible and/or irreversible MPD. Analysis of MPI allowed the identification of 122 patients with negative MPI and 83 with positive MPI. MPD were more prevalent and irreversible nature in 6A homozygotes than 5A MMP3 allele carries (MPD – 6A6A: 52.6%, 5A allele: 37.4%, p>0.05; irreversible MPD – 6A6A: 34.2%, 5A allele: 19.6%, p>0.05). All 6A homozygote patients with myocardial infarction or those who underwent coronary revascularisation had MPD (p < 0.05). Analysis of logistic regression revealed the 6A6A genotype and combined 6A6A+CT/TT genotypes such as genetic risk factors for myocardial ischaemia [Model 1, adjusted conventional risk factors 6A6A: odds ratio (OR) = 1.85, 6A6A+T allele: OR = 1.55; [Model 2, adjusted haemodynamic risk factors 6A6A: OR = 1.29, 6A6A+T allele: OR = 1.73; p>0.05, non-unique contribution). The results of this study suggest that the allelic variation of MMP3 gene can have an important role in myocardial remodelling, and appoint the 6A6A genotype as a marker of alterations in myocardial blood perfusion, especially remodelling associated with irreversible MPD. This study also showed that the allelic variation of MMP9 gene had no significant influence in myocardial perfusion.