İndolamin 2, 3 dioksijenaz (IDO) gen polimorfizminin COVİD-19 ve kliniği üzerine etkisi
Loading...
Date
2021-01-25
Authors
Karaca, Mert
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Pandemi olarak ilan edilmiş, küresel bir sorun teşkil eden COVID-19 hastalığına, koronavirüs ailesinden SARS-CoV-2 virüsü ile enfeksiyonun neden olduğu bilinmektedir. İnsan bağışıklık sisteminin bu virüse karşı verdiği tepkiler halen anlaşılmaya çalışılmaktadır. Bu araştırmada önemli bir immünmodülatör olan IDO (indoleamine 2-3-dioxygenase)’nun COVID-19 üzerindeki etkilerinin araştırılması amaçlanmıştır. Çalışmamızın tasarlanmasında, SARS-CoV virüsünün özellikleri ve COVID-19’un klinik tablosu ile IDO’nun özellikleri ve diğer viral enfeksiyonlar ile ilişkileri göz önünde bulundurulmuştur. IDO gen bölgelerinde görülen polimorfizmlerin inflamatuvar epizodlarda etkili olduğu da bilinmektedir. Bu doğrultuda, IDO-1 ve IDO-2 için belirlenen iki ayrı IDO SNP gen bölgelesinde, 40 hasta için melting curve analizi ile tek nükleotid polimorfizm (SNP) tespiti yapılmıştır. Ek olarak serum örneklerinde ELISA yöntemiyle Th1, Th2, Th17 ilişkili bazı sitokin ve IDO-1 konsantrasyonları saptanarak, sitokinlerin IDO-1 seviyeleri ile korelasyonları incelenmiştir. Yapmış olduğumuz tek nükleotid polimorfizm çalışmamızın sonucunda; IDO-1 rs7820268 SNP bölgesinin COVID-19 hastalığına yatkınlıkla ilişkili olduğu sonucu elde edilmiştir. Bu SNP bölgesi için elde edilen sonuçlar üzerine yapmış olduğumuz analizler sonucunda, yatkınlık dışında, patogenez ile bir ilişki saptanamamıştır. IDO-2 için incelenen rs4503083 SNP bölgesinde ise hasta ve sağlıklı kontrol grubu ile anlamlı farklılık tespit edilmemiştir. ELISA sonuçlarımız da ise; IL-6 ve TNF-α ile IDO-1 arasında negatif yönlü korelasyonlar saptanmıştır. Önemli olarak, SARS-CoV-2 virüsünün diğer viral enfeksiyonların aksine IDO-1’i baskıladığı tespit edilmiştir. Yoğun bakım hastalarında, asemptomatik hastalardan daha düşük seviyelerde IDO-1 konsantrasyonu görülmüştür. Tez çalışma sonuçlarımız IDO’yu COVID-19 prognozu için terapötik hedef olarak önermektedir.
The virus that causes COVID-19 disease is the SARS-CoV-2 virus from the coronavirus family, and people infected with this virus have the disease. This disease is a global problem and has been reported as a pandemic.The reaction of the human immune system to the COVID-19 virus is not well understood yet. In this study, it was aimed to reveal the importance of IDO (indoleamine 2-3-dioxygenase), which is an important immunomodulator, on the virus. In the design of our the study, the clinical course of COVID-19 and the characteristics of the SARS-CoV virus and the connection between IDO and other viral infections should be considered. The effect of polymorphisms in IDO gene regions on inflammatory conditions is also known. Considering these important issues, single nucleotide polymorphism (SNP) was analyzed with melting curve analysis in two different IDO SNP gene regions determined for IDO-1 and IDO-2 for 40 patients. Relationships between Th1, Th2, Th17-related cytokines and IDO-1 concentrations and IDO-1 levels of cytokines were investigated in serum samples by ELISA. As a result of the single nucleotide polymorphism study; The IDO-1 rs7820268 SNP region was determined to be associated with susceptibility to COVID-19 disease. In the analysis of the results obtained on the SNP region, it was found that there was a predisposition, but that there was not a relationship with pathogenesis. The rs4503083 SNP region was examined for IDO-2, no significant difference was found between the patient and healthy control groups. According to the ELISA results, it was observed that there was a negative correlation between IL-6 and TNF-α, and IDO-1. The important issue found in the study was that the SARS-CoV-2 virus suppressed IDO-1 unlike other viral infections. The IDO-1 levels were found to be lower in intensive care patients compared to asymptomatic patients. According to the results of the study, IDO can be recommended as a complementary marker for the diagnosis of COVID-19. Also, it may be therapeutic target for the treatment of the disease.
The virus that causes COVID-19 disease is the SARS-CoV-2 virus from the coronavirus family, and people infected with this virus have the disease. This disease is a global problem and has been reported as a pandemic.The reaction of the human immune system to the COVID-19 virus is not well understood yet. In this study, it was aimed to reveal the importance of IDO (indoleamine 2-3-dioxygenase), which is an important immunomodulator, on the virus. In the design of our the study, the clinical course of COVID-19 and the characteristics of the SARS-CoV virus and the connection between IDO and other viral infections should be considered. The effect of polymorphisms in IDO gene regions on inflammatory conditions is also known. Considering these important issues, single nucleotide polymorphism (SNP) was analyzed with melting curve analysis in two different IDO SNP gene regions determined for IDO-1 and IDO-2 for 40 patients. Relationships between Th1, Th2, Th17-related cytokines and IDO-1 concentrations and IDO-1 levels of cytokines were investigated in serum samples by ELISA. As a result of the single nucleotide polymorphism study; The IDO-1 rs7820268 SNP region was determined to be associated with susceptibility to COVID-19 disease. In the analysis of the results obtained on the SNP region, it was found that there was a predisposition, but that there was not a relationship with pathogenesis. The rs4503083 SNP region was examined for IDO-2, no significant difference was found between the patient and healthy control groups. According to the ELISA results, it was observed that there was a negative correlation between IL-6 and TNF-α, and IDO-1. The important issue found in the study was that the SARS-CoV-2 virus suppressed IDO-1 unlike other viral infections. The IDO-1 levels were found to be lower in intensive care patients compared to asymptomatic patients. According to the results of the study, IDO can be recommended as a complementary marker for the diagnosis of COVID-19. Also, it may be therapeutic target for the treatment of the disease.
Description
Keywords
IDO, COVID-19, SARS-CoV-2, SNP, İmmünoloji, Enfeksiyon, Immunology, Infection
Citation
Karaca, M. (2021). İndolamin 2, 3 dioksijenaz (IDO) gen polimorfizminin COVİD-19 ve kliniği üzerine etkisi. Yayınlanmamış yüksek lisans tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.