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Angiotensin II Type I Receptor—168A/G Polymorphism Is Associated with Increased the Risk of Glioma in Turkish Population

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Abstract

Gliomas are the most common primary tumors of the Central Nervous System. Despite advances in the elucidation of molecular pathogenesis, gliomas still remain incurable. In the study, it was aimed to investigate the possible connection between ACE and AGTR1 polymorphisms with glioma pathogenesis and also the relationship of some angiogenic markers with gliomagenesis. In this respect, 96 glioma patients and 104 healthy controls were included in the study. To determine the effect of genetic polymorphisms on the predisposition of diffuse infiltrative glial tumors in the Turkish population, angiotensin-converting enzyme gene (ACE) insertion/deletion, angiotensin II receptor type 1 gene (AGTR1) ‒168A/G, ‒535C/T, ‒825T/A, and Vascular Endothelial Growth Factor gene (VEGF) +936C/T, ‒2578C/A polymorphisms were investigated by PCR-RFLP. Allele/genotype frequencies between patients and controls were determined. Besides, relative gene expressions of ACE, AGTR1, and VEGF were detected by real time-PCR, while ACE, VEGF, ET-1, eNOS, and NO levels were measured in both serum and tissue by ELISA. In AGTR1 ‒168A/G polymorphism, the risk of glioma in the AA genotype decreased, while increased by 2.27 times in the G allele. Allele frequency and genotype distributions of other polymorphisms were found similar between two groups. Serum levels of ACE, VEGF, eNOS, NO, and tissue levels of ACE, ET-1, eNOS, NO were also different between the patients and controls. ACE, AGTR1, and VEGF expressions in patient group were found significantly higher than in control one. These results provide the first evidence linking ‒168A/G polymorphism in AGTR1 gene with glioma risk in the Turkish population.

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DATA AVAILABILITY

The datasets generated during and analyzed during the current study will be available from the corresponding author upon reasonable request.

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ACKNOWLEDGMENTS

The authors would like to thank Prof. Ali Ergül and Umut Kibar for their contribution to primer design and selection of restriction enzymes and assistance in Real-Time PCR applications.

Funding

This study was supported financially by the Scientific and Technological Research Council of Turkey (TÜBİTAK; project no. 216S995).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey

    T. Turan & A. Gönenç

  2. Department of Neurosurgery, Faculty of Medicine, Gazi University, 06500, Ankara, Turkey

    B. Özaydın, Ö. H. Emmez & A. M. Kaymaz

  3. Department of Neurological Surgery, University of Wisconsin-Madison School of Medicine and Public Health, 8660, Madison, WI, USA

    B. Özaydın

  4. Department of Medical Pathology, Faculty of Medicine, Gazi University, 06500, Ankara, Turkey

    İ. I. Gönül

  5. Department of Neurosurgery, Faculty of Medicine, İstanbul Arel University, 34537, İstanbul, Turkey

    M. Bozkurt

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Contributions

TT: Conceptualization, Formal Analysis, Investigation, Roles/Writing—Original Draft.

BÖ: Resources, Roles/Writing—Original Draft.

ÖHE: Conceptualization, Methodology, Resources, Supervision, Writing—Review & Editing.

AMK: Resources.

İIG: Investigation, Resources, Validation, Writing— Review & Editing.

MB: Resources.

AG: Conceptualization, Formal analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Supervision, Writing—Review & Editing.

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Correspondence to A. Gönenç.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was approved by the Clinical Research Ethics Committee of Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital with the decision number 189 dated December, 2015. All procedures involving people comply with the ethical standards of the institutional and/or national committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards. Informed written consent was achieved from all subjects included in the study according to the ethical standards of the Ethics Committee.

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Abbreviations: CNS, Central Nervous System; ACE, Angiotensin Converting Enzyme; I/D, Insertion/Deletion; AGTR1, Angiotensin II Type I Receptor; AGTR2, Angiotensin II Type II Receptor; VEGF, Vascular Endothelial Growth Factor; NO, Nitric Oxide; ET-1, Endothelin-1; eNOS, Endothelial Nitric Oxide Synthase; WHO, World Health Organization; PCR-RFLP, Polymerase Chain Reaction Restriction Fragment Length Polymorphism; Touch down-PCR, Touch Down Polymerase Chain Reaction; UV, Ultraviolet; RE, Restriction Enzyme; PBS, Phosphate Buffer; PASS, Power Analysis and Sample Size.

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Turan, T., Özaydın, B., Emmez, Ö.H. et al. Angiotensin II Type I Receptor—168A/G Polymorphism Is Associated with Increased the Risk of Glioma in Turkish Population. Mol Biol 58, 216–232 (2024). https://doi.org/10.1134/S0026893324020158

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