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Genetic polymorphisms in VEGFA and VEGFR2 genes associated with coronary heart disease susceptibility and severity

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Abstract

Background

​Vascular endothelial growth factor A (VEGFA) is well acknowledged as a powerful angiogenesis-promoting agent mainly through its receptor VEGFR2. Ischemia stimulates VEGFA/VEGFR2 signaling pathway and elevated serum levels of VEGFA were detected in coronary heart disease (CHD) patients. The goal of the current study is to determine how four SNPs in the genes for VEGFA (rs3025039 and rs699947) and VEGFR2 (rs2305948 and rs1870377) contribute to the development of CHD. We also wanted to use the Gensini score to confirm if these four SNPs have an effect on the severity of coronary lesions.

Methods

In this case-control research, we used the restriction fragment length polymorphism of the polymerase chain reaction to genotype 239 CHD patients and 200 controls. Age, sex, smoking behavior, and obesity were taken into account in the statistical analysis.

Results

Two VEGFA/VEFGR2 signaling pathway SNPs (rs699947 and rs1870377) were found to be associated with CHD (C vs. A, P = 0.002; OR = 1.47 (1.12–1.93); A vs. T, P = 0.001; OR = 1.58 (1.17–2.13) respectively). The rs2305948 showed no allelic associations with CHD susceptibility, although we noticed a slight association under the recessive model of rs3025039 TT genotype (p = 0.023; OR = 6.41 (1.14–36.12)) only under adjusted analyses. In addition, both VEGFA SNPs (rs699947and rs3025039) were found to be associated with high Gensini score (p < 0.001).

Conclusions

Our research helps to shed further light on the pathophysiology of CHD. The VEGFA/VEGFR2 signaling pathway may have been downregulated, increasing CHD susceptibility and risk.

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Data Availability

Data relating to the study results are available on request from the corresponding author.

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Acknowledgements

The authors are grateful to the patients and volunteers for their collaboration, the entire team for collecting blood samples from patients (Cardiology Department and Hematology department at Fattouma Bourguiba Hospital, University of Monastir, Tunisia).

Funding

Our study was funded by research organizations in Tunisia (Ministry of Public Health and Ministry of Higher Education and Scientific Research).

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Authors and Affiliations

  1. Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, Monastir, Tunisia

    Foddha Hajer, Chouchene Saoussen, Bouzidi Nadia, Dhiflaoui Ameni, Ben abdennebi Hassen & Haj Khelil Amel

  2. Laboratory of Genetics, Biodiversity and Bioresource Valorization (LR11ES41), Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia

    Saoud Hana

  3. Department of Hematology, Fattouma Bourguiba Hospital, University of Monastir, Monastir, Tunisia

    Chouchene Saoussen

  4. Cardiology Department, Fattouma Bourguiba Hospital, University of Monastir, Monastir, Tunisia

    Foddha Abdelhak & Gamra Habib

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  1. Foddha Hajer
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  2. Saoud Hana
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  3. Chouchene Saoussen
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Contributions

All authors contributed to the study conception and design. Conceptualization, methodology, formal analysis and investigation were performed by: Foddha hajer. Material preparation, data collection were performed by: Chouchene Saoussen, Bouzidi Nadia, Dhiflaoui Ameni, Gamra Habib, and Ben abdennebi Hassen. The first draft of the manuscript was written by: Foddha hajer and Foddha Abdelhak. Correction of the draft and supervision were performed by: Haj Khelil Amel. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Foddha Hajer.

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Authors declare that they have no conflict of interest and that there are no financial or non-financial interests that are directly or indirectly related to this work.

Statement of ethics

This work is part of a study indexed under the number NCT03373552 of clinical trials on the site of the NIH (National Institutes of Health) of the United States “ClinicalTrials.gov”.

Informed consent

Written informed consent was obtained from each patient included in the study. All research was performed in accordance with ethical guidelines of the 1975 Declaration of Helsinki and the study protocol has been priorly approved by the Institution’s ethics committee on research on humans.

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Hajer, F., Hana, S., Saoussen, C. et al. Genetic polymorphisms in VEGFA and VEGFR2 genes associated with coronary heart disease susceptibility and severity. Mol Biol Rep 50, 10169–10177 (2023). https://doi.org/10.1007/s11033-023-08899-z

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