title: Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair.
abstract: 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.
authors.affiliation: Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China. xfcheung@hkucc.hku.hk
authors.forename: Yiu-fai
authors.initials: YF
authors.lastname: Cheung
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Hong
authors.forename: Koon-wing
authors.initials: KW
authors.lastname: Chan
authors.forename: Sophia J
authors.initials: SJ
authors.lastname: Wong
mesh_terms: D000483:Alleles; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D004247:DNA / Q000235:genetics; D004452:Echocardiography; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D011110:Polymorphism, Genetic; D013771:Tetralogy of Fallot / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D014655:Vascular Resistance / Q000235:genetics; D059289:Vascular Stiffness / Q000235:genetics*; D055815:Young Adult
chemical_list: D004247:DNA; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9