Investigation of the putative functional relevance of the IL-6 3'UTR genetic variants with athletic phenotype in Turkish triathletes

Abstract

Previous research suggests that genetic variants in the interleukin-6 (IL-6) gene contribute to sport-related traits and athletic performance. We aimed to identify sequence variants in the IL-6 gene region comprising the 3' untranslated region (UTR) in the Turkish triathletes and sedentary individuals and assessed their putative roles in tendency to athletic phenotype. Sequence variants were identified in the Turkish triathletes (n = 47) and sedentary individu-als (n = 46) by Sanger sequencing. Allele/genotype frequencies and linkage disequilibrium (LD) patterns were calculated by the Haploview program. The functional significance of the detected variants was analyzed using in silico prediction tools. Four single nucleotide vari-ants (rs13306435, rs747302620, rs2069849, rs13306436) were detected in saliva samples of the participants by sequencing the target region. Notably, rs13306436-3'UTR/IL-6 was only seen in the triathletes, while the exonic rs747302620 was observed in only sedentary group. Also, rs13306436G>A causes loss/gain sites for binding multiple miRNAs that may be associated with athletic performance. Our findings indicate that the 3'UTR/IL-6 may have functional relevance in determining sports talent. Future comprehensive studies focusing on the IL-6 gene in athletes may pave the way for not only determining the athletic status of the individuals but also have implications for translational medicine.

Keywords

• 3'UTR
• bioinformatics
• SNV
• sport genetics
• Interleukin-6
• Triathletes

Öz

Önceki araştırmalar, interlökin-6 (IL-6) geni varyantlarının spor ile ilgili özelliklere ve atle-tik performansa katkı sağladığını ileri sürmektedir. Bu çalışmada, Türk triatletler ve sedanter bireylerde IL-6 geninin 3' translasyon olmayan bölgelerinde (UTR) dizi varyantlarını tanım-lamayı ve bunların atletik fenotipe yatkınlıktaki varsayılan rollerini değerlendirmeyi amaçla-dık. Türk triatletlerde (n = 47) ve sedanter bireylerde (n = 46) dizi varyantları Sanger dizi-leme ile tanımlanmıştır. Alel/genotip frekansları ve bağlantı dengesizliği (LD) örüntüleri Haploview programı ile hesaplanmıştır. Tespit edilen varyantların fonksiyonel önemleri in silico tahmin araçları kullanılarak analiz edilmiştir. Hedef gen bölgesinin dizilenmesi sonu-cunda, katılımcıların tükürük örneklerinde dört tek nükleotid varyantı (rs13306435, rs747302620, rs2069849, rs13306436) tespit edilmiştir. rs13306436-3'UTR/IL-6 sadece triatletlerde görülürken, ekzonik rs747302620 sadece sedanter grupta gözlenmiştir. Ayrıca, rs13306436G>A, miRNA'ların bağlanabileceği kayıp/kazanç bölgeleri yaratarak atletil per-formans ile ilişkili olabilir. Bulgularımız, 3'UTR/IL-6'nın sporcu yeteneğini belirlemede iş-levsel bir öneme sahip olabileceğini göstermektedir. Sporcularda IL-6 genine odaklı yapıla-cak gelecekteki kapsamlı çalışmalar, yalnızca bireylerin atletik durumlarının belirlenmesine değil, aynı zamanda translasyonel tıp için de çıkarımlara yol açabilir.

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