Determination of Deleterious SNPs in NUDT15 Gene Related to Acute Lymphoblastic Leukemia by using Bioinformatics Tools

Deniz Aşlar Öner

Makale detayları

Determination of Deleterious SNPs in NUDT15 Gene Related to Acute Lymphoblastic Leukemia by using Bioinformatics Tools

Yazarlar:

Deniz Aşlar Öner

Yayıncı:

İstanbul Gelisim University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi Issue 21, pp.866-880

Belge Tipi:

Makale

Yayın Tarihi:

5/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001308753

pISSN:

2536-4499

Anahtar kelimeler:

Özet:

 Aim: In acute lymphoblastic leukemia ALL, thiopurine group drugs are the most basic drugs and are included in almost all treatment protocols, especially in maintenance treatment. The mechanism of action of thioguanine nucleotides is to enter the DNA structure in cells, disrupt DNA synthesis, and trigger programmed cell death. The impact of deleterious SNPs on nucleotide triphosphate diphosphatase protein regarding ALL is not yet fully understood. In this study, it was aimed to determine the possible deleterious impacts of missense variants in the NUDT15 gene on protein structure and stabilization that play a significant role in susceptibility to the disease, using modern bioinformatics software. Method: To access SNPs in the NUDT15, it was used National Center for Biotechnology Information NCBI, Single Nucleotide Polymorphism Database dbSNP. In bioinformatics tools used in this study included SIFT, PolyPhen-2, PROVEAN, SNAP2, and PANTHER, followed by I-Mutant, HOPE, and STRING. Results: The results of the analysis showed that in a total of 6663 SNPs in the NUDT15, 6 variants have been identified as deleterious. According to the I-Mutant software, 4 deleterious SNPs decreased protein stability while 2 deleterious SNPs increased protein stability. In the HOPE database analysis, E115G, E57G, F52L, and K33N mutant amino acids were found to be smaller and more hydrophobic than wild-type amino acids, while G53R and G145D mutant amino acids were found to be larger. Thus, all variations resulted in alterations in the net charge on the NUDT15 protein. Conclusion: Data on NUDT15 variants will contribute to the prediction of the patients response to thiopurine drugs in future studies, to a better understanding of the patients susceptibility to drug interactions, and ultimately to obtaining information about the prognosis.

 Aim: In acute lymphoblastic leukemia ALL, thiopurine group drugs are the most basic drugs and are included in almost all treatment protocols, especially in maintenance treatment. The mechanism of action of thioguanine nucleotides is to enter the DNA structure in cells, disrupt DNA synthesis, and trigger programmed cell death. The impact of deleterious SNPs on nucleotide triphosphate diphosphatase protein regarding ALL is not yet fully understood. In this study, it was aimed to determine the possible deleterious impacts of missense variants in the NUDT15 gene on protein structure and stabilization that play a significant role in susceptibility to the disease, using modern bioinformatics software. Method: To access SNPs in the NUDT15, it was used National Center for Biotechnology Information NCBI, Single Nucleotide Polymorphism Database dbSNP. In bioinformatics tools used in this study included SIFT, PolyPhen-2, PROVEAN, SNAP2, and PANTHER, followed by I-Mutant, HOPE, and STRING. Results: The results of the analysis showed that in a total of 6663 SNPs in the NUDT15, 6 variants have been identified as deleterious. According to the I-Mutant software, 4 deleterious SNPs decreased protein stability while 2 deleterious SNPs increased protein stability. In the HOPE database analysis, E115G, E57G, F52L, and K33N mutant amino acids were found to be smaller and more hydrophobic than wild-type amino acids, while G53R and G145D mutant amino acids were found to be larger. Thus, all variations resulted in alterations in the net charge on the NUDT15 protein. Conclusion: Data on NUDT15 variants will contribute to the prediction of the patients response to thiopurine drugs in future studies, to a better understanding of the patients susceptibility to drug interactions, and ultimately to obtaining information about the prognosis.

 Aim: In acute lymphoblastic leukemia ALL, thiopurine group drugs are the most basic drugs and are included in almost all treatment protocols, especially in maintenance treatment. The mechanism of action of thioguanine nucleotides is to enter the DNA structure in cells, disrupt DNA synthesis, and trigger programmed cell death. The impact of deleterious SNPs on nucleotide triphosphate diphosphatase protein regarding ALL is not yet fully understood. In this study, it was aimed to determine the possible deleterious impacts of missense variants in the NUDT15 gene on protein structure and stabilization that play a significant role in susceptibility to the disease, using modern bioinformatics software. Method: To access SNPs in the NUDT15, it was used National Center for Biotechnology Information NCBI, Single Nucleotide Polymorphism Database dbSNP. In bioinformatics tools used in this study included SIFT, PolyPhen-2, PROVEAN, SNAP2, and PANTHER, followed by I-Mutant, HOPE, and STRING. Results: The results of the analysis showed that in a total of 6663 SNPs in the NUDT15, 6 variants have been identified as deleterious. According to the I-Mutant software, 4 deleterious SNPs decreased protein stability while 2 deleterious SNPs increased protein stability. In the HOPE database analysis, E115G, E57G, F52L, and K33N mutant amino acids were found to be smaller and more hydrophobic than wild-type amino acids, while G53R and G145D mutant amino acids were found to be larger. Thus, all variations resulted in alterations in the net charge on the NUDT15 protein. Conclusion: Data on NUDT15 variants will contribute to the prediction of the patients response to thiopurine drugs in future studies, to a better understanding of the patients susceptibility to drug interactions, and ultimately to obtaining information about the prognosis.

 Amaç: Akut lenfoblastik lösemide ALL tiopurin grubu ilaçlar en temel ilaçlardır ve idame tedavisi başta olmak üzere hemen hemen tüm tedavi protokollerinde yer almaktadır. Tiyoguanin nükleotitlerinin etki mekanizması hücrelerde DNA yapısına girmek, DNA sentezini bozmak ve programlı hücre ölümünü tetiklemektir. Zararlı tek nükleotid polimorfizmlerin SNPlerin ALL ile ilgili nükleotid trifosfat difosfataz proteini üzerindeki etkisi henüz tam olarak anlaşılmamıştır. Bu çalışmada, NUDT15 genindeki yanlış anlamlı varyantların hastalığa yatkınlıkta önemli rol oynayan protein yapısı ve stabilizasyonu üzerine olası zararlı etkilerinin modern biyoinformatik yazılımları kullanılarak belirlenmesi amaçlanmıştır. Yöntem: NUDT15 genindeki SNPlere erişmek için Ulusal Biyoteknoloji Bilgi Merkezi NCBI, Tek Nükleotid Polimorfizm Veritabanı dbSNP kullanılmıştır. Bu çalışmada SIFT, PolyPhen-2, PROVEAN, SNAP2, PANTHER, I-Mutant, HOPE ve STRING biyoinformatik araçlarının kullanımı yer almıştır. Bulgular: Analiz sonuçları, NUDT15 genindeki toplam 6663 SNPde 6 varyantın zararlı olarak tanımlandığını göstermiştir. I-Mutant yazılımına göre 4 zararlı SNP protein stabilitesini azaltırken 2 zararlı SNP protein stabilitesini arttırmıştır. HOPE veri tabanı analizinde E115G, E57G, F52L ve K33N mutant amino asitlerinin yabanıl tip amino asitlere göre daha küçük ve hidrofobik olduğu, G53R ve G145D mutant amino asitlerinin ise daha büyük olduğu tespit edilmiştir. Bu sebeple, tüm varyasyonlar NUDT15 proteini üzerindeki net yükte değişiklikle sonuçlanmıştır. Sonuç: NUDT15 varyantlarına ilişkin veriler, gelecekteki çalışmalarda hastanın tiopürin ilaçlarına yanıtının tahmin edilmesine, hastanın ilaç etkileşimlerine duyarlılığının daha iyi anlaşılmasına ve nihayetinde prognoz hakkında bilgi edinilmesine katkı sağlayacaktır.

Makale detayları

Determination of Deleterious SNPs in NUDT15 Gene Related to Acute Lymphoblastic Leukemia by using Bioinformatics Tools

Yazarlar:

Deniz Aşlar Öner

Yayıncı:

İstanbul Gelisim University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi Issue 21, pp.866-880

Belge Tipi:

Makale

Yayın Tarihi:

5/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001308753

pISSN:

2536-4499

Leukemia

single nucleotide polymorphism

thiopurineLösemi

tek nükleotid polimorfizm

tiyopurin

Sayı

Makale detayları

Determination of Deleterious SNPs in NUDT15 Gene Related to Acute Lymphoblastic Leukemia by using Bioinformatics Tools

Yazarlar: Deniz Aşlar Öner

Yayıncı: İstanbul Gelisim University

Ana Başlıklar: Klinik Tıp Bilimleri

Dergi: İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi Issue 21, pp.866-880

Belge Tipi: Makale

Yayın Tarihi: 5/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001308753

pISSN: 2536-4499

Leukemia

single nucleotide polymorphism

thiopurineLösemi

tek nükleotid polimorfizm

tiyopurin

Sayı

Yazarlar:

Deniz Aşlar Öner

Yayıncı:

İstanbul Gelisim University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi Issue 21, pp.866-880

Belge Tipi:

Makale

Yayın Tarihi:

5/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001308753

pISSN:

2536-4499