title: Promoter polymorphism of the matrix metalloproteinase 3 gene is associated with regurgitation and left ventricular remodelling in mitral valve prolapse patients.
abstract: OBJECTIVE
  Mitral valve prolapse (MVP) is common and highly variable in its severity, but the factors underlying this variability are unclear. In this study, we tested the hypothesis that polymorphic variations in Matrix Metalloproteinase (MMP) genes might be predictors of left ventricular (LV) remodelling and severity of regurgitation in MVP.
  
  
  RESULTS
  70 MVP patients and 75 normal subjects were studied. We performed comprehensive echocardiography and analyzed promoter polymorphisms in the MMP-1 and MMP-3 genes. The MMP-3 -1612 5A/6A polymorphism showed strong associations with indices of mitral regurgitation and LV remodelling: Patients with 5A/5A allele had more pronounced remodelling and more severe mitral regurgitation than patients with the 6A/6A or 5A/6A alleles. We then cloned and sequenced 2 kb fragments of MMP-3 promoter from patients with 5A/5A and 6A/6A genotypes and found 4 different sets of promoter haplotypes. Promoter analysis showed that higher promoter activity was related to a more severe phenotype and that the haplotype variants had a more dominant role in determining the activity.
  
  
  CONCLUSIONS
  Our data identifies the MMP-3 promoter haplotype as a novel marker of an adverse disease course in MVP, suggesting the presence of genetic determinants for the severity of MVP.
authors.affiliation: Division of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. delvac.oceandy@manchester.ac.uk
authors.forename: Delvac
authors.initials: D
authors.lastname: Oceandy
authors.forename: Rahal
authors.initials: R
authors.lastname: Yusoff
authors.forename: Florence M
authors.initials: FM
authors.lastname: Baudoin
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
authors.forename: Simon G
authors.initials: SG
authors.lastname: Ray
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008945:Mitral Valve Prolapse / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1