Şizofreni hastalarında CYB mtDNA mutasyonları ve PI3K/AKT/mTOR sinyal yolağındaki genlerin ekspresyon durumu

Year 2022, Volume: 47 Issue: 4, 1695 - 1708, 28.12.2022

Ebubekir Dirican , Sevgi Karabulut Uzunçakmak , Halil Özcan

https://doi.org/10.17826/cumj.1186118

Cited By: 1

Abstract

Amaç: Bu çalışma, şizofreni hastalarında sitokrom b (CYB) mitokondriyal DNA (mtDNA) mutasyonlarını taramayı ve PI3K/AKT/mTOR sinyal yolağındaki genlerin mRNA ifadelerini analiz etmeyi amaçlamıştır.
Gereç ve Yöntem: Bu çalışmada 44 şizofreni hastasından ve 41 sağlıklı bireyden DNA (hasta) ve RNA (hasta ve kontrol) izolasyonu için tam kan alındı. CYB mtDNA mutasyonları için örnekler PCR ile amplifiye edildi ve Sanger DNA dizi analiziyle tanımlandı. PIK3CA, AKT1 ve mTOR genlerinin mRNA ekspresyonu için RT-PCR ve 2-∆∆Ct metodu kullanıldı.
Bulgular: Şizofreni hastalarında m.15326 A>G (43/44), m.15452 C>A (5/44), m.15078 A>G (3/44), m.14872 C>T (3/44) ve m.14798 T>C (3/44) en sık rastalanan CYB mtDNA mutasyonlarıydı. İn silico analizler, mutasyonların bir kısmının zararlı, hastalık yapıcı veya benign karakterle ilişkili olduğunu gösterdi. Şizofreni hastalarında PIK3CA, AKT1 ve mTOR genlerinin mRNA ekspresyonu sağlıklı bireylere göre anlamlı derecede yüksekti. PIK3CA ve AKT1 genleri arasında anlamlı orta şiddette pozitif bir korelasyon tespit edildi. Ayrıca ROC analizi ile PIK3CA, AKT1 ve mTOR genlerinin hasta grubunda iyi tanısal güce sahip olduğu belirlendi. ROC analizleri, özellikle PIK3CA'nın şizofreni hastaları için % 80 duyarlılık ve % 63,4 seçicilik ile önemli bir tanı değerine sahip olduğunu gösterdi.
Sonuç: Şizofreni hastalarında hem CYB mtDNA mutasyon sıklığı hem de PIK3CA, AKT1 ve mTOR mRNA ekspresyon düzeyi sağlıklı bireylere göre daha yüksekti. Bu mekanizmaları daha geniş şizofreni popülasyonunda çalışmanın hastalığın tanı, tedavi veya prognozunda değerli olabileceğine inanıyoruz.

Keywords

Şizofreni, mtDNA, CYB, PI3K, AKT, mTOR

CYB mtDNA mutations and expression status of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia

Abstract

Purpose: This study aimed to screen for cytochrome b (CYB) mitochondrial DNA (mtDNA) mutations and analyze the mRNA expressions of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia.
Materials and Methods: In this study, whole blood was obtained from 44 schizophrenic patients and 41 healthy individuals for DNA (patients) and RNA (patients and control) isolation. Samples for CYB mtDNA mutations were amplified by PCR and identified by Sanger DNA sequencing. RT-PCR and 2-∆∆Ct method was used for mRNA expression of PIK3CA, AKT1, and mTOR genes.
Results: In schizophrenia patients, m.15326 A>G (43/44), m.15452 C>A (5/44), m.15078 A>G (3/44), m.14872 C> T (3/44) and m.14798 T>C (3/44) was the most common CYB mtDNA mutations. In silico analysis showed that some of the mutations were associated with the harmful, disease-causing or benign character. The mRNA expression of the PIK3CA, AKT1, and mTOR genes in schizophrenia patients was significantly higher than in healthy individuals.There was a significant moderate positive correlation between the PIK3CA and AKT1 genes. In addition, by ROC analysis, PIK3CA, AKT1 and mTOR genes were found to have good diagnostic power in the patient group. ROC analyzes showed that PIK3CA in particular has significant diagnostic value for schizophrenia patients with 80% sensitivity and 63.4% specificity.
Conclusion: Both of CYB mtDNA mutations frequency and PIK3CA, AKT1 and mTOR mRNA expression were higher in schizophrenic patients compared to healthy individuals. We believe that studying these mechanisms in the larger schizophrenia population may be valuable in the diagnosis, treatment, or prognosis of the disease.

Keywords

Schizophrenia, mtDNA, CYB, PI3K, AKT, mTOR

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