二尖瓣脱垂/二尖瓣脱垂综合征（FMV/MVP）患者的基质金属蛋白酶多态性

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

作者信息

Lima Sarah M, Pitsis Antonios A, Kelpis Timotheos G, Shahin Mohamed H, Langaee Taimour Y, Cavallari Larisa H, Theofilogiannakos Efstratios K, Boudoulas Harisios, Boudoulas Konstantinos Dean

机构信息

Division of Cardiovascular Medicine, Department of Medicine, The Ohio State University, Columbus, OH, USA.

出版信息

Cardiology. 2017;138(3):179-185. doi: 10.1159/000477656. Epub 2017 Jul 28.

DOI:10.1159/000477656

PMID:28750369

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.

摘要

背景

有研究表明，二尖瓣脱垂（FMV）/二尖瓣反流（MVP）患者存在二尖瓣胶原异常。这些患者中决定胶原合成和降解的遗传因素尚未明确。本研究旨在确定对胶原周转有已知或推测作用的基质金属蛋白酶-2（MMP2）或转化生长因子-β（TGFβ）的选择性多态性在FMV/MVP患者中是否更常见。

方法

在98例患有严重二尖瓣反流的FMV/MVP患者中测定与胶原周转相关的特定基因中的单核苷酸多态性（SNP），包括MMP2 rs2285053、MMP2 rs243865、TGFβ1 rs1800469和TGFβ2 rs900，并与99例对照进行比较。

结果

与对照组相比，MMP2 rs243865是唯一与FMV/MVP显著相关的SNP（优势比2.07，95%可信区间1.23 - 3.50，p = 0.006）。与无该综合征的FMV/MVP患者相比，MMP2 rs228503是唯一与FMV/MVP综合征显著相关的SNP（优势比2.41，95%可信区间1.08 - 5.40，p = 0.032）。