Key result
The MMP-3 5A/5A genotype was associated with more pronounced left ventricular remodelling and more severe mitral regurgitation compared to the 6A/6A or 5A/6A alleles in MVP patients.
Why the study?
Are MMP-1 and MMP-3 gene promoter polymorphisms associated with left ventricular remodelling and severity of regurgitation in patients with mitral valve prolapse?
Case-Control (n=145)
Are MMP-1 and MMP-3 gene promoter polymorphisms associated with left ventricular remodelling and severity of regurgitation in patients with mitral valve prolapse?
The MMP-3 promoter haplotype is identified as a novel genetic marker associated with an adverse disease course, including more severe regurgitation and LV remodelling, in patients with mitral valve prolapse.
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.
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Oceandy et al. (2007) conducted a case-control in Mitral valve prolapse (n=145). MMP-3 -1612 5A/5A genotype vs. 6A/6A or 5A/6A genotypes was evaluated on Severity of mitral regurgitation and left ventricular remodelling. The MMP-3 5A/5A genotype was associated with more pronounced left ventricular remodelling and more severe mitral regurgitation compared to the 6A/6A or 5A/6A alleles in MVP patients.
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