Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair.

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix proteins, which are important determinants of arterial stiffness. This study aimed to test the hypothesis that MMP-3 and MMP-9 polymorphisms may modulate aortic stiffness and magnitude of aortic root dilation in patients after surgical repair of tetralogy of Fallot (TOF). We analyzed the MMP-3 promoter and MMP-9 -1562 C>T polymorphism in 79 TOF patients aged 19.9 ± 9.5 years and determined their associations with aortic stiffness and sinotubular dimension. Genotypic and allelic frequencies of MMP-3 for the 6A6A genotype and MMP-9 for the T allele did not differ between patients and published control data (all p>0.05). For the MMP-3 locus, patients with a 6A6A genotype and those with a 6A6A/5A6A genotype had similar aortic stiffness (p=0.60), heart-femoral pulse wave velocity (p=0.63), and z score of sinotubular junction (p=0.81). For the MMP-9 locus, the -1562T allele carriers had significantly lower aortic stiffness (p=0.005), slower heart-femoral pulse wave velocity (p=0.03), and smaller z score of sinotubular junction (p=0.047). Multivariate linear regression identified MMP-9 polymorphism (β=-0.31, p=0.005) as a significant correlate of aortic stiffness after adjustments for age at study, age at operation, sex, body mass index, systolic and diastolic blood pressures, and MMP-3 polymorphism. In conclusion, MMP-9 but not MMP-3 polymorphism exerts a modulating influence on aortic stiffness and aortic root dilation in patients after TOF repair.