The relationship of the gene polymorphisms of matrix metalloproteinase-1, -2, -3 and -9 to the progression of coronary atherosclerotic plaque / 介入放射学杂志

ABSTRACT

Objective To evaluate the influence of the gene polymorphisms of matrix metalloproteinase(mmp)-1 ,-2,-3 and -9 on coronary atherosclerotic plaque progression. Methods During the period of January 2005-December 2008, 80 patients with coronary heart disease underwent two times coronary angiography at authors' hospital. Based on the angiographic findings, the patients were classified into plaque progression group (n = 31 ) and plaque non-progression group (n = 49). Coronary atheroselerotic plaque progression was arbitrarily defined as that the minimal lumen diameter (MLD) of coronary artery showed a decrease ≥ 0.4 mm on the second coronary angiography. The detailed history and clinical examination results were collected, including serum concentrations of lipid profiling, fasting glucose and hs-CRP. Genotypings for polymorphic variances of MMP-1 (-1607 G/GG), MMP-2 (-955 A/C), MMP-3 (-1612 5A/6A ) and MMP-9 (-1562 C/T) were performed by polymerase chain reaction (PCR) and sequencing analysis in two groups.Comparison of the clinical characteristics and polymorphisms between two groups was made to assess their effects on coronary atherosclerotic plaque progression. Results More female patients and patients with acute coronary syndrome (ACS) were noted in patients with plaque progression compare to those with no progression (41.9% vs. 18.4%, P < 0.05 and 77.4% vs. 46.3%, P < 0.01, respectively).The serum hs-CRP level also significantly increased in group with plaque progression (0.26 ± 0.44 mg/L vs.0.02 ± 0.14 mg/L, P < 0.01). Multivariable logistic regression analysis revealed that serum hs-CRP concentration and ACS were independent risk factors of coronary atherosclerotic plaque progression (OR12.63,95% CI1.45-110.29, P < 0.05 and OR2.99,95% CI1.04-8.63, P < 0.05, respectively). The frequencies of 6A/6A genotype and 6A allele of MMP-3 promoter at location -1612 were significantly higher in group with plaque progression than that in group with no progression (87.1% vs. 53.1%, P < 0.01 and 93.5% vs. 75.5%, P < 0.01, respectively). However, no significant differences in the distribution of MMP-1,-2 and -9 polymorphisms existed between two groups. Conclusion ACS, feminine gender, high serum hs-CRP concentration and 5A/6A polymorphism in the MMP-3 gene promoter are closely associated with coronary atherosclerotic plaque progression. In addition, 5A/6A polymorphism of MMP-3 can be used as a marker for plaque progression.