title: Matrix metalloproteinase-1 mitral expression and -1607 1G/2G gene promoter polymorphism in mitral chordae tendinae rupture.
abstract: Understanding the pathogenesis of mitral chordae tendinae rupture (MCTR) is essential for identification of risk factors. Mitral matrix metalloproteinase (MMP) triggers the signal cascade that instigates cardiac fibrosis, which may be a predisposing factor in MCTR. We investigated associations among MMP1 expression, MMP1 -1607 1G/2G polymorphism and mitral chordae tendinae rupture (MCTR). This study enrolled 185 patients (group A) receiving mitral valve replacement. Group A included 65 patients with MCTR and 120 controls without MCTR. MMP1 was assessed on a semiquantitative scale (0-3) by immunohistochemical staining. For genetic association study, another 227 subjects were recruited for group B, including 75 with MCTR and 152 controls. The gene polymorphisms were analyzed by polymerase chain reaction. In group A, MCTR patients had a higher MMP1 expression compared to controls (P < 0.001). Binary regression analysis showed the variation in the MCTR patients was independently explained by MMP1 (P = 0.027). Hypertension and MMP1 staining had a synergistic effect on the MCTR occurrence (P < 0.001). In group B, MMP1 -1607 1G allele was increased in patients with MCTR compared to controls (P = 0.014). The odds ratio for the 1G/1G genotype to the 2G/2G genotype was 3.22 (P = 0.009). Univariate and logistic regression analysis showed an independent association between MCTR and MMP1 -1607 1G/2G polymorphism (P = 0.028 and 0.032, respectively). Since MMP1 mitral expression and -1607 1G/2G polymorphism were associated with MCTR independently of other baseline characteristics, MMP1 may play a role in the individual susceptibility to MCTR.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Chaw-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Ho-Ming
authors.initials: HM
authors.lastname: Su
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Wang
authors.forename: Wen-Chol
authors.initials: WC
authors.lastname: Voon
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002815:Chordae Tendineae / Q000000981:diagnostic imaging / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006341:Heart Rupture / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000150:complications; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D008943:Mitral Valve / Q000000981:diagnostic imaging / Q000201:enzymology; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D057170:Translational Research, Biomedical; D014463:Ultrasonography
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1