Reference : Promoter polymorphism of the matrix metalloproteinase 3 gene is associated with regur...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/10993/18370
Promoter polymorphism of the matrix metalloproteinase 3 gene is associated with regurgitation and left ventricular remodelling in mitral valve prolapse patients.
English
Oceandy, Delvac [> >]
Yusoff, Rahal [> >]
Baudoin, Florence M. [> >]
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Ray, Simon G. [> >]
2007
European journal of heart failure
9
10
1010-7
Yes (verified by ORBilu)
International
1388-9842
Netherlands
[en] Aged ; Alleles ; Case-Control Studies ; Female ; Heart Ventricles/pathology/ultrasonography ; Humans ; Hypertrophy, Left Ventricular/genetics ; Male ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 3/genetics ; Middle Aged ; Mitral Valve Insufficiency/genetics/pathology/ultrasonography ; Mitral Valve Prolapse/genetics/pathology/ultrasonography ; Polymorphism, Genetic ; Promoter Regions, Genetic/genetics ; Ventricular Remodeling/genetics
[en] BACKGROUND AND AIMS: 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. METHODS AND 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.
http://hdl.handle.net/10993/18370
10.1016/j.ejheart.2007.07.005
http://onlinelibrary.wiley.com/doi/10.1016/j.ejheart.2007.07.005/abstract;jsessionid=EB7EAC736523D47542FB2E7E10EF6A17.f02t03

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