Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi

Abstract

Giriş: CTLA-4 (sitotoksik T-lenfosit ilişkili antijen 4) geni, immünoglobulin gen süper ailesinin bir üyesidir ve T hücrelerine inhibe edici bir sinyal ileten proteini kodlamaktadır. Son günlerde immün kontrol noktası olan CTLA-4 geni araştırılan genler arasındadır. Bu çalışmada amaç; CTLA-4 geninde oluşan çeşitli polimorfizmlerin, CTLA-4 geni ile benzer genlerin Otoimmün Tiroid Hastalığı (OTH) patogenezine katkıda bulunabileceğini in silico olarak değerlendirmektir.
Gereç ve Yöntem: Çalışmamızda CTLA-4 geni ile benzer genleri bulmak için GeneMania ve STRING veri tabanları, tek nükleotid polimorfizmlerini (SNP’leri) bulmak için Polyphen2, Exome Variant Server ve SIFT veritabanları, mikro RNA’ları tespit etmek için; miRDB ve miRWalk veritabanları kullanıldı.
Bulgular: Çalışmamızdan elde ettiğimiz verilere göre; FYN geninin OTH’nın patogenezine katkıda bulunabileceğini, CTLA-4 geniyle ilişkili (rs201778935, rs138279736, rs369567630 ve rs376038796) şüpheli SNP’lerin olduğunu tespit ettik.
Sonuç: Çalışmamızda 31 miRNA’nın mesajcı RNA’ların protein üretmesini düzenleyici rol üstlendiğinden, terapötik açıdan önemli olduğunu düşünmekteyiz. Biyoinformatik yöntemlerle değerlendirdiğimiz bu çalışma, ilerde laboratuvar ortamında uygulanarak, birçok hastalığın patogenezinin aydınlatılmasına katkıda bulunabileceğini düşünmekteyiz.

Keywords

• CTLA-4,
• in silico,
• miRNA,
• SNP,
• biyoinformatik

Evaluation of the in silico analysis of CTLA-4 gene in autoimmune thyroid diseases

Abstract

Introduction: CTLA-4 (cytotoxic T-lymphocyte associated antigen-4) gene is a member of the immunoglobulin gene superfamily, encoding the protein that transmits an inhibiting signal to T cells. The CTLA-4 gene is an immune checkpoint  among the genes being investigated  nowadays. The aim of this study was to find  various polymorphisms in the CTLA-4 gene may contribute to the pathogenesis of autoimmune thyroid disease (AITD) by investigating the genes that are similar to the CTLA-4 gene.
Material and Method: In our study, we used GeneMania and STRING databases to find similar genes with CTLA-4 gene, then we used Polyphen2, Exome Variant Server and SIFT databases to find single nucleotide polymorphisms (SNPs), miRDB and miRWalk databases were used to detect micro RNAs in the CTLA-4 gene. According to our results, we found that the FYN gene may contribute to the pathogenesis of AITD. 
Results: We  discovered SNPs (rs201778935, rs138279736, rs369567630 and rs376038796) that are associated with the CTLA-4 gene. In our study, we have thought that 31 miRNAs are therapeutically important, they play a regulatory role in the production of proteins by messenger RNAs.
Conclusion: We believe that this study, which we evaluated with bioinformatics methods, can contribute to  the explanation of  the pathogenesis of many disease by performing lab based experiments in the future.

Keywords

• CTLA-4
• in silico
• miRNA
• SNP
• biyoinformatik

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