title: Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients.
abstract: OBJECTIVE
  Bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly which affects 0.5-2% of the population. It can be associated with other cardiac congenital lesions such as aortic aneurysms or aortic coarctation. Some genetic abnormalities have been suggested as the underlying cause of BAV and aortic root dilatation, but no clear genetic substrate and no specific pathogenic gene variant have already been identified. Increased matrix metalloproteinase activity has been described in the aortic wall of thoracic aortic aneurysms (TAA).
  
  
  METHODS
  87 patients with BAV and 77 controls with normal tricuspid aortic valve were prospectively assessed. We analysed three functional polymorphisms (-1607 1G/2G, -519 A/G, and -340 T/C) in the matrix metalloproteinase (MMP)-1 gene using polymerase chain reaction and restriction fragment length analysis.
  
  
  RESULTS
  We found a haplotype composed of the lower activity allele from each polymorphism (-1607 1G/-519 A/-340 C) significantly less frequent in BAV group (p=0.016; OR [95% CI]=0.37 [0.16-0.85]), association even more clear when we consider only men (p=0.0005, OR [95% CI]=0.24 [0.10-0.56]). We also found a borderline statistical significance in the distribution of the -1607 alleles, being 2G allele more frequent in patients with TAA (p=0.053). This association was stronger and statistically significant when we consider only men (p=0.013; OR [95% CI]=2.0 [1.16-3.50]). In addition, genotype -1607 2G2G, theoretically the more active transcriptionally, was also significantly more frequent in TAA group, independently of aortic valve morphology.
  
  
  CONCLUSIONS
  Our study suggests that specific genotypes of MMP1 gene could be in part responsible of the complications of BAV pathology, like TAA.
authors.affiliation: Cardiology Department-Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain. mmartinf7@hotmail.com
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.forename: Irene A
authors.initials: IA
authors.lastname: Pichel
authors.forename: Juan P
authors.initials: JP
authors.lastname: Flórez Muñoz
authors.forename: Manuel
authors.initials: M
authors.lastname: Naves-Díaz
authors.forename: María
authors.initials: M
authors.lastname: Palacín
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Cannata-Andía
authors.forename: César
authors.initials: C
authors.lastname: Morís
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
mesh_terms: D000368:Aged; D000483:Alleles; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D001021:Aortic Valve / Q000002:abnormalities / Q000201:enzymology; D000082882:Bicuspid Aortic Valve Disease; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006349:Heart Valve Diseases / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D014158:Transcription, Genetic; D044465:White People / Q000235:genetics
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1