Background: Mediators involved in atherosclerosis and plaque rupture may have importance as risk markers for coronary artery disease (CAD). We have investigated the influence of matrix metalloproteinase (MMP)-9 genetic variations on gene- and protein expression in stable CAD patients.
Methods: The promoter -1562C/T and exon 6 R279Q A/G polymorphisms were determined in 1001 patients with angiographically verified stable CAD and in 204 healthy controls. Genotype and gene-expression were determined by real-time PCR. Serum levels of MMP-9 and its inhibitor TIMP-1were measured immunologically and by zymography (MMP-9 activity).
Results: None of the polymorphisms associated with the presence of CAD, myocardial infarction or type 2 diabetes, whereas the variant allele of the R279Q polymorphism associated with hypertension (adjusted p=0.015). The T- and G alleles associated with lower and higher mRNA levels, respectively (p<0.005 both), also shown in an experimental ex-vivo LPS stimulated model. T-allele carriers had higher concentrations of MMP-9 (adjusted p=0.032) and the GG genotype induced lower MMP-9 gelatinolytic activity (p=0.01). Higher MMP-9 gene-expression and TIMP-1 levels were observed in patients with previous myocardial infarction, the latter also was elevated in diabetics (<0.05, all).
Conclusion: The investigated MMP-9 polymorphisms influenced gene- and protein expression differently and the R279Q polymorphism associated significantly with hypertension.
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