Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome

Abstract

Background: It has been suggested that collagen abnormalities of the mitral valve are present in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP). Genetic factors determining collagen synthesis and degradation have not been well defined in these patients. This study was undertaken to determine whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or transforming growth factor-β (TGFβ), with known or putative effects on collagen turnover, are more frequent in FMV/MVP. Methods: Single nucleotide polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2 rs2285053, MMP2 rs243865, TGFβ1 rs1800469, and TGFβ2 rs900, were determined in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to 99 controls. Results:MMP2 rs243865 was the only SNP significantly associated with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p = 0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio 2.41, 95% CI 1.08-5.40, p = 0.032). Conclusion: The frequency of certain MMP2 polymorphisms is higher in patients with the FMV/MVP syndrome and patients with FMV/MVP without the syndrome. The data suggest that a genetic predisposition that alters collagen turnover may play a role in the pathogenesis and development of FMV/MVP.

The Potential of Intertwining Gene Diagnostics and Surgery for Mitral Valve Prolapse

“…Comparing the genotype distributions and allele frequencies of MMP-SNPs between patients affected by MVD and healthy controls revealed a significant association between the occurrence of MMP-SNPs and MVD [56]. Moreover, the MMP2 rs243865 SNP has been closely correlated with the occurrence of MVP specifically [57].…”

Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis

“…Like FlnA mutations, alterations to the ECM change cytoskeletal structure and function which can result in pathological signaling and remodeling. Erk activity specifically localizes to regions of matrix metallopeptidase 2 expression ( 213 ), an ECM degrading enzyme, which is significantly increased in clinical patients with floppy mitral valves and mitral valve prolapse ( 214 ). A variety of collagen mutations result in mitral valve prolapse, aortic root dilation, and a host of structural defects ( 215 , 216 ).…”