NF-KB, TLR-4 ve TLR-2 varyasyonlarının glioma ile ilişkilerinin incelenmesi /
Yazar: İDRİS KINA
Danışman: PROF. DR. ALİ NUR TURGUT ULUTİN
İstanbul Üniversitesi / Sağlık Bilimleri Enstitüsü / Tıbbi Biyoloji Ana Bilim Dalı
Derece: Yüksek Lisans, 2017
Konu: Tıbbi Biyoloji = Medical Biology
Dizin: Beyin neoplazmları = Brain neoplasms ; Gen ifadesi = Gene expression ; Genler = Genes ; Glioma = Glioma ; Neoplazmlar = Neoplasms ; Nükleer faktör-kappa B = Nuclear factor-kappa B ; Polimorfizm-genetik = Polymorphism-genetic ; Reseptörler-toll like = Receptors-toll like

Özet:
Gliomalar,  merkezi  sinir  sisteminde  (MSS)  bulunan  glial  hücrelerden  geliş
en  ve  tüm MSS tümörlerinin % 40'dan fazlasında tanımlanan en yaygın primer beyin tümörleridir. Hucre ici sinyal yolaklarinin kanser biyolojisinde kritik rol oynadigi
 iyi bilinmektedir. NFKB  ve  TLR  sinyal  yolaklari  aktivasyonunun  kanser  riskindeki  onemi ortaya konmasina ragmen,  bu  genlerdeki  polimorfizmler  ile  glioma  arasindaki  iliski  henuz acikliga kavusturulmamistir.Bu çalışmada NF-kB-94 ins/del ATTG, TLR-4 Asp299Gly, TLR-4 Thr399Ile ve TLR-2 Arg753Gln gen  polimorfizmleri  ile  glioma  riski  arasindaki  iliskiyi  arastirmayi amacladik.  Calisma,  120  glioma  hastası  ve  225  saglikli  kontrol  grubu  ile gerceklestirildi.  Genotip  dagilimlari  polimeraz  zincir  reaksiyonu-restriksiy on  parca uzunluk polimorfizmi (PCR-RFLP) yontemi ile saptandi. 
Glioma  ve  kontrol  grubundaki  NF-kB-94  ins/del  ATTG, TLR-4 Asp299Gly,  TLR-4 Thr399Ile
ve  TLR-2 Arg753Gln polimorfizmlerine  ait  genotip  dagilimlari karsilastirdigimizda, NF-kB -94 ins/ins genotipinin glioma  icin risk  faktoru oldugunu gosterdik (p=0,003). Diger yandan, TLR-2753 GG genotipinin glioma gelişimine karşı koruyucu rol oynadigini
saptadık (p=0,001). Ayrica, TLR-2 Arg753Gln polimorfizmi icin A allelinin glioma gelisimine karsi koruyucu rol oynadigini saptadik (p<0,001). Bu bulgulara ek olarak, TLR-4 299 AG genotipi ile azalmis glioma riski arasinda anlamli bir iliski saptadik (p<0,001). TLR-4 Thr399Ile polimorfizmi acısından hasta ve kontrol grubu arasinda herhangi bir anlamlı ilişki saptamadık (p>0, 05). Bu  bulgular  NF-KB  ve  TLR  sinyal  yolaklarindaki  polimorfizmlerin  glioma  riskinde onemli bir rol oynayabilecegini gostermektedir. 

Anahtar Kelimeler: NF-KB, TLR, glioma, polimorfizm

Abstract:
Gliomas are the most common primary brain tumors that develop from glial cells in the central nervous system (CNS) and are identified in more than 40% of all CNS tumors. Cellular signaling pathways play a critical role in cancer biology. Although the activation of NFKB and TLR signaling pathways is well known for cancer risk, the association between polymorphisms in these genes and glioma has not yet been elucidated. In this study, our aim was to study the relationship between NF-kB-94 ins/del ATTG, TLR-4 Asp299Gly, TLR-4 Thr399Ileand TLR-2 Arg753Gln polymorphisms
and glioma risk. The study was conducted with 120 glioma patients and 225 control groups. Genotype distributions were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical data were analyzed by IBM SPSS 20, Chi-Square test and Combined Genotype analysis. When we compared the genotype distributions of the polymorphisms of NF-kB-94 ins/del ATTG, TLR-4 Asp299Gly, TLR-4 Thr399Ileand TLR-2 
Arg753Gln in glioma and control groups, we found risk factors of NF-kB -94 ins/ins genotype for glioma (p=0.003). On the other hand, we found that TLR-4 299Gg genotype might be associated with a protective effect against development of glioma (p=0.001). Furthermore, we showed that TLR-2 753 A allele was significantly associated with the decreased risk of glioma (p<0.001). In addition to these findings, we observed an association between decreased risk of glioma TLR-4 299 AG genotype (p<0.001). However, we did not reveal any markedly association between patients and controls in terms of TLR-4 399 polymorphism (p>0.05). These findings show that polymorphisms of NF-KB and TLR signal pathways can play a critical role for glioma risk.
Key words: NF-KB, TLR, glioma, polymorphism