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.

中文翻译：

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血管紧张素 II I 型受体 — 168A/G 多态性与土耳其人群患神经胶质瘤的风险增加相关

摘要

神经胶质瘤是中枢神经系统最常见的原发性肿瘤。尽管分子发病机制的阐明取得了进展，但神经胶质瘤仍然无法治愈。本研究旨在探讨ACE和AGTR1多态性与胶质瘤发病机制之间的可能联系，以及一些血管生成标志物与胶质瘤发生的关系。在这方面，该研究纳入了 96 名神经胶质瘤患者和 104 名健康对照者。为了确定土耳其人群中遗传多态性对弥漫性浸润性神经胶质瘤易感性的影响，血管紧张素转换酶基因 ( ACE ) 插入/缺失、血管紧张素 II 受体 1 型基因 ( AGTR1 ) –168A/G， –535C/T通过PCR-RFLP研究了-825T/A和血管内皮生长因子基因( VEGF )+936C/T、-2578C/A多态性。确定患者和对照之间的等位基因/基因型频率。此外，实时荧光定量PCR法检测ACE、AGTR1、VEGF的相对基因表达量，ELISA法测定血清和组织中ACE、VEGF、ET-1、eNOS、NO的水平。在AGTR1-168A /G多态性中，AA基因型的胶质瘤风险降低，而G等位基因的胶质瘤风险增加2.27倍。发现两组之间其他多态性的等位基因频率和基因型分布相似。患者和对照组之间的ACE、VEGF、eNOS、NO的血清水平和ACE、ET-1、eNOS、NO的组织水平也存在差异。患者组ACE、AGTR1、VEGF表达显着高于对照组。这些结果提供了第一个证据，将AGTR1基因的 168A/G 多态性与土耳其人群的神经胶质瘤风险联系起来。