ESC Heart Failure (Jun 2023)

Association between MMP2 gene polymorphisms and dilated cardiomyopathy in a Chinese Han population

  • Shiyang Li,
  • Xiaobin Zeng,
  • Shihai Wang,
  • Xiaoshuang Xie,
  • Jianjun Lan

DOI
https://doi.org/10.1002/ehf2.14333
Journal volume & issue
Vol. 10, no. 3
pp. 1793 – 1802

Abstract

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Abstract Aims Dilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc‐dependent and calcium‐containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. Methods and results A total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865‐C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P < 0.05). Besides, rs243865‐C allele presented a correlation with the poor prognosis of DCM patients in both dominant (HR = 2.0, 95% confidence interval [CI] = 1.14–3.57, P = 0.017) and additive (HR = 1.85, 95% CI = 1.09–3.13, P = 0.02) model. The statistical significance remained after adjustment for sex, age, hypertension, diabetes, hyperlipidaemia, and smoking status. There were significant differences in left ventricular end‐diastolic diameter and left ventricular ejection fraction between rs243865‐CC and CT genotypes. Functional analysis indicated that rs243865‐C allele increased luciferase activity and the mRNA expression level of MMP2 by facilitating ZNF354C binding. Conclusions Our study suggested that MMP2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese Han population.

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