Research Information System
Thesis Type: Doctorate
Institution Of The Thesis: Gazi University, Sağlık Bilimleri Enstitüsü, Biyokimya (Ecz) Anabilim Dalı, Turkey
Approval Date: 2019
Thesis Language: Turkish
Student: TAYLAN TURAN
Supervisor: Aymelek Gönenç
Abstract:
Gliomas are the most common primary tumors of CNS. Despite the advance in the
elucidation of the molecular pathogenesis of these tumors, glioma still remains incurable.
ACE and AGTR1 polymorphism are the focal points for various cancer studies, both in
relation to cancer pathogenesis and its relationship with metastasis and angiogenesis. There
are many studies on the relationship between ACE and AGTR1 polymorphism and cancer
pathogenesis in various types of cancer in different populations. However, the results
obtained from these studies are in contradiction when compared to each other. In this
thesis, it was aimed to find out the possible connection between ACE, AGTR1
polymorphism and glioma pathogenesis and also the relationship between some angiogenic
markers which will be measured in both serum and tissue, and angiogenesis. 96 glioma
patients and 104 healthy controls with mean age 49,09±1,33 and 48,60±1,34 were included
in the study. ACE I/D, AGTR1 -168A/G, AGTR1 -535C/T, AGTR1 -825T/A, VEGF
+936C/T and VEGF -2578C/A polymorphisms were investigated in the thesis by PCRRFLP
method. By this means, allele and genotype frequencies between patients and
healthy controls were determined. Relative gene expressions of ACE, AGTR1 and VEGF
were determined by Real Time-PCR while, the levels of parameters that are associated
with angiogenesis such as ACE, VEGF, ET-1, eNOS and NO were measured in both
serum and tissue by using ELISA method. As a conclusion, in AGTR1 -168A/G
polymorphism, the risk of glioma of AA genotype decreased significantly, G allele
increased the risk of glioma by 2,27 times. Allele frequency and genotype distributions of
ACE I/D, AGTR1 -535C/T, -825T/A, VEGF +936C/T and VEGF -2578C/A
polymorphisms were found to be similar distribution between patient and control groups.
Serum ACE, VEGF, eNOS, NO and tissue ACE, ET-1, eNOS, NO values were also
significantly different between the patient and healthy control groups. ACE, AGTR1 and
VEGF gene expressions of the patient group were found to be significantly higher than the
control group. The presence of high tumor risk in G allele in AGTR1 polymorphism,
increased serum levels and gene expression of ACE in glioma shed light on the
development of tumor in terms of ACE and ACE receptor polymorphism.
Key Words : Glioma, Polymorphism, ACE, AGTR1, Angiogenesis, Real Time PCR