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Matrix metalloproteinase 3 and 9 as genetic biomarkers for the occurrence of cardiovascular complications in coronary artery disease: a prospective cohort study

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Abstract

Background

Matrix metalloproteinases (MMPs) are widely expressed in atherosclerosis lesions. The disequilibrium of MMPs driving to an overexpression or a lack of its level can be influenced by genetic variations. MMP-3 and MMP-9 may be affected by specific polymorphisms like − 1612 5 A/6A and the − 1562 C/T respectively. We aim in the present study to investigate prospectively the association between the − 1612 5 A/6A MMP-3 and − 1562 C/T MMP-9 polymorphisms and clinical outcomes in patients with coronary artery disease (CAD). This study is elaborated to reveal whether one of these polymorphisms is a probable predictor of cardiovascular complications in this CAD cohort.

Methods and Results

A total of 168 patients with CAD were prospectively followed up over a period of 5 years. Genotypes for the MMP-3 (-1612 5 A/6A) and MMP-9 (-1562 C/T) polymorphisms were performed using PCR-RFLP. Their levels were measured by ELISA in Sandwich test during the follow-up period, 39 cardiovascular outcomes occurred with 21 repeat targets for revascularization, 3 patients with Myocardial infarction, 8 for heart failure, 5 for Stroke and 2 for cardiovascular mortality. The MMP-3 5 A/6A polymorphism was related to the disease on the contrary of the MMP-9 -1562 C/T. Patients carrying the 5 A allele had a higher level of MMP-3 level and those who carried the 6 A allele had lower level (p = 0.04). After applied multivariable Cox-hazard models we revealed that the 6 A allele is independently associated to the disease complication. Kaplan–Meier survival test revealed that individuals having the 6 A allele had a lower survival rate than those with the 5 A allele (p = 0.04).

Conclusion

Our study suggests the disruption of the MMP-3 level may be due to the existence of the polymorphism − 1612 residing in its promoter region. MMP-3 can be considered as a marker of diagnosis and prediction in cardiovascular events.

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Authors and Affiliations

  1. LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia

    Imen Guizani, Wiem Zidi, Yosra Zayani, Fourti Nesrine, Haifa Sanhaji, Moncef Feki & Monia Allal-Elasmi

  2. Cardiology Department, CHU la Rabta, 1007, Jebbari Tunis, Tunisia

    Mohamed Sami Mourali

  3. Faculty of Mathematics, Physics and Natural Sciences, University of Tunis El Manar, Tunis, Tunisia

    Imen Guizani

  4. LR99ES10 Human Genetics Laboratory, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

    Hayet Douik

  5. Laboratory of Biochemistry, La Rabta Hospital, 1007, Jebbari, Tunis, Tunisia

    Monia Allal-Elasmi

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  1. Imen Guizani
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Correspondence to Monia Allal-Elasmi.

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The study was supported by a grant from the “Ministry of High Education, Scientific Research and Technologies of Tunisia”.

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The survey protocol was approved by the ethics committee for human research of La Rabta Hospital and corresponds to the declaration of Helsinki 1975 ethical guidelines. All participants gave their informed consent.

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Guizani, I., Zidi, W., Zayani, Y. et al. Matrix metalloproteinase 3 and 9 as genetic biomarkers for the occurrence of cardiovascular complications in coronary artery disease: a prospective cohort study. Mol Biol Rep 49, 9171–9179 (2022). https://doi.org/10.1007/s11033-022-07742-1

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