INTER-POPULATION COMPARISONS AND THE IMPORTANCE IN INFECTIOUS DISEASES OF THE IRF7, TBK1, IFNAR1, IFNAR2 AND TLR3 GENE VARIANTS IN TURKISH INDIVIDUALS

Öz

Objective: In the research conducted during the pandemic period, it has been determined that IRF7, TBK1, IFNAR1, IFNAR2, and TLR3 immunity genes play an important role in the predisposition to SARS-CoV-2 infection. However, there is no information about variants of these genes in the Turkish population. The aim of this study was to determine the variants specific to the our study’s population in these genes that predispose to infections and to compare them with other populations.
Materials and Methods: The variants in the exonic and flanking intronic regions of these five genes were analysed in in-house whole-exome sequencing data of 139 unrelated non-anonymous individuals. The allele frequencies of variants were compared with other population datasets. The DysGeNet database was used to determine human diseases associated with these genes.
Results: In our population, gene variants were detected including 28 in IRF7, 16 in TBK1, 18 in IFNAR1, 19 in IFNAR2, and 9 in TLR3. The allele frequencies of variants were compared with other populations. Of these variants, 9 were determined to be novel, previously unreported variants. It was shown that these genes are mainly involved in cancer and infectious diseases, especially viral infections according to the DisGeNET database. Conclusion: The determination of immunity gene variants specific to our population and the variability of allele frequencies among populations suggest that it may cause differences in immune response, especially to SARS-CoV-2 infection. In this study, preliminary information was obtained for studies that will investigate the relationship between the clinical manifestations of infectious diseases and immunity gene variants.

Anahtar Kelimeler

• Infectious diseases
• population
• immunity genes
• variant

TÜRK POPÜLASYONUNDA IRF7, TBK1, IFNAR1, IFNAR2 VE TLR3 GEN VARYANTLARININ POPÜLASYONLAR ARASI KARŞILAŞTIRMALARI VE ENFEKSİYON HASTALIKLARINDAKİ ÖNEMİ

Öz

Amaç: Halen devam etmekte olan pandemi sürecinde yapılan araştırmalarda, IRF7, TBK1, IFNAR1, IFNAR2 ve TLR3 immünite genlerinin SARS-CoV-2 enfeksiyona yatkınlıkta önemli rol oynadıkları belirlenmiştir. Ancak, Türk popülasyonunda bu genlerdeki varyantlar ile ilgili detaylı bilgi bulunmamaktadır. Bu çalışmada, enfeksiyonlara yatkınlık oluşturan bu genlerdeki toplumumuza özgü varyantların belirlenmesi ve diğer popülasyonlarla karşılaştırılması amaçlandı.
Gereç ve Yöntem: IRF7, TBK1, IFNAR1, IFNAR2 ve TLR3 genlerindeki ekzonik ve komşu intronik bölgelerdeki gen varyantları, 139 anonim bireye ait kurum içi tüm ekzom dizileme verilerinde analiz edildi. Varyantların allel sıklıkları, diğer popülasyonların veri setleri ile karşılaştırıldı. Ek olarak, literatürdeki bu 5 aday gen ile ilişkili hastalıkları belirlemek için DisGeNET veri tabanı kullanıldı.
Bulgular: Toplumumuzdaki immünite gen varyantları belirlenerek allel sıklıkları diğer popülasyonlar ile karşılaştırıldı. Buna göre IRF7 geninde 28, TBK1’de 16, IFNAR1’de 18, IFNAR2’de 19, TLR3’de 9 varyant tespit edildi. Bu varyantlardan dokuzunun daha önce bildirilmemiş yeni varyant oldukları belirlendi. DisGe- NET veri tabanına göre, bu genlerin çoğunlukla kanser ve enfek- siyon hastalıklarında özellikle viral enfeksiyonlarla ilgili oldukları gösterildi. Sonuç: Toplumuza özgü immünite gen varyantlarının belirlen- mesi ve popülasyonlar arasında allel sıklıklarının değişkenlik göstermesi, özellikle SARS-CoV-2 enfeksiyonuna immün yanıtta farklılıklara sebep olabileceğini düşündürmektedir. Bu çalışma- da, enfeksiyon hastalıklarının klinik bulguları ile immünite gen varyantları arasındaki ilişkiyi araştıracak çalışmalar için önbilgiler elde edilmiştir.

Anahtar Kelimeler

• Enfeksiyon hastalıkları
• popülasyon
• immünite genleri
• varyant

Kaynakça

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