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Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi

Yıl 2020, Cilt 1, Sayı 3, 58 - 63, 21.09.2020
https://doi.org/10.47582/jompac.739257

Öz

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.

Kaynakça

  • Brunet JF, Denizot F, Luciani MF, et al. A new member of the immunoglobulin superfamily CTLA-4. Nature 1987; 328: 267-70.
  • He F, Zhou Y, Wang X, et al. Functional Polymorphisms of CTLA-4 associated with aggressive periodontitis in the Chinese Han population. Cell Physiol Biochem 2018; 50: 1178-85.
  • Li L, Liu J, Qin S, Li R. Correlation between CTLA-4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion: A case-control study. Medicine (Baltimore) 2018 ; 97: e12754.
  • Yao L, Liu B, Jiang L, Zhou L, Liu X. Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children. Hematology 2019; 24: 123-8.
  • Pistillo MP, Fontana V, Morabito A, et al. Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma inter group study. Cancer Immunol Immunother 2019; 68: 97-07.
  • Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev 2008; 224: 166–82.
  • Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 2007; 7: 95-06.
  • Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity 1996; 4: 535-43.
  • Esensten HJ, Helou AY, Chopra G, Weiss A, Bluestone AJ. CD28 costimulation: from mechanism to therapy. Immunity 2016; 17: 973-88.
  • Kristiansen OP, Larsen ZM. CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity. Genes Immun 2000; 1: 170-84.
  • Douroudis K, Prans E, Uibo R. CTLA-4 promoter polymorphisms are associated with latent autoimmune diabetes in adults. Hum Immunol 2009; 70: 921-4.
  • Hunt KA. A common CTLA-4 haplotype associated with coeliac disease. Eur J Hum Genet 2005; 13: 440-4.
  • Shojaa M. Association between 318C/T polymorphism of the CTLA-4 gene and systemic lupus erythematosus in Iranian patients. Int J Rheum Dis 2017; 20: 2040-4.
  • Online Mendelian Inheritance in Man. https://omim.org/. (Erişim Tarihi: 09.04.2020) .
  • National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/. (Erişim Tarihi: 09.04.2020)
  • NCBI-SNP. https://www.ncbi.nlm.nih.gov/snp/. (Erişim Tarihi: 09.04.2020)
  • Franz M, Rodriguez H, Lopes C, et al. GeneMANIA update 2018. Nucleic Acids Res 2018; 46: 60-4.
  • Mering VC, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 2003; 31: 258-61.
  • Mutarelli M, Marwah V, Rispoli R, et al. A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders. BMC Genomics 2014; 15: S5.
  • Sim LN, Kumar P, Hu J, Henikoff S, Schneider G, Pauline C. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res 2012: 40: 452-7.
  • Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013; 76: 7-20.
  • Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 2015; 28: 146-52.
  • Dweep H, Sticht C, Pandey P, Gretz N. miRWalk database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 2011; 44: 839-47.
  • Brunner MC, Chambers CA, Chan FK, Hanke J, Winoto A, Allison JP. CTLA-4-Mediated inhibition of early events of T cell proliferation. J Immunol 1999; 162: 5813-20.
  • Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016; 39: 98-106.
  • Piccirillo CA, Shevach EM. Naturally-occurring CD4 + CD25 + immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 2004; 16: 81-8.
  • Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000; 192: 303-9.
  • Chen K, Kolls JK. Interluekin-17A. Gene 2017; 30: 8-4.
  • Kim CH. FOXP3 and its role in the immune system. Adv Exp Med Biol 2009; 665: 17-9.
  • Ganesh BB, Bhattacharya A, Gopisetty A, Prabhakar BS. Role of cytokines in the pathogenesis and suppression of thyroid autoimmunity. J Interferon Cytokine Res 2011; 31: 721-31.
  • Hu Y, Zhang L, Chen H, et al. Analysis of regulatory T cell subsets and their expression of helios and PD-1 in patients with hashimoto thyroiditis. Int J Endocrinol 2019; 2019: 5368473.
  • Watanabe A, Inoue N, Watanabe M, et al. Increases of CD80 and CD86 Expression on peripheral blood cells and their gene polymorphisms in autoimmune thyroid disease. Immunol Invest 2020; 49: 191-203.
  • Caio RDC, Quaio Jozélio F, Carvalho Clovis A, Bueno CS Amanda S. Autoimmune disease and multiple autoantibodies in 42 patients with RA Sopathies. Am J Med Genet A 2012; 158A: 1077-82.
  • Li J, Zhou H. Fyn gene polymorphisms contribute to both trait and state anxieties in healthy Chinese-Han individuals. Psychiatr Genet 2012; 22: 312-3.
  • Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res 2016; 7: 68-74.

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

Yıl 2020, Cilt 1, Sayı 3, 58 - 63, 21.09.2020
https://doi.org/10.47582/jompac.739257

Öz

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.

Kaynakça

  • Brunet JF, Denizot F, Luciani MF, et al. A new member of the immunoglobulin superfamily CTLA-4. Nature 1987; 328: 267-70.
  • He F, Zhou Y, Wang X, et al. Functional Polymorphisms of CTLA-4 associated with aggressive periodontitis in the Chinese Han population. Cell Physiol Biochem 2018; 50: 1178-85.
  • Li L, Liu J, Qin S, Li R. Correlation between CTLA-4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion: A case-control study. Medicine (Baltimore) 2018 ; 97: e12754.
  • Yao L, Liu B, Jiang L, Zhou L, Liu X. Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children. Hematology 2019; 24: 123-8.
  • Pistillo MP, Fontana V, Morabito A, et al. Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma inter group study. Cancer Immunol Immunother 2019; 68: 97-07.
  • Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev 2008; 224: 166–82.
  • Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 2007; 7: 95-06.
  • Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity 1996; 4: 535-43.
  • Esensten HJ, Helou AY, Chopra G, Weiss A, Bluestone AJ. CD28 costimulation: from mechanism to therapy. Immunity 2016; 17: 973-88.
  • Kristiansen OP, Larsen ZM. CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity. Genes Immun 2000; 1: 170-84.
  • Douroudis K, Prans E, Uibo R. CTLA-4 promoter polymorphisms are associated with latent autoimmune diabetes in adults. Hum Immunol 2009; 70: 921-4.
  • Hunt KA. A common CTLA-4 haplotype associated with coeliac disease. Eur J Hum Genet 2005; 13: 440-4.
  • Shojaa M. Association between 318C/T polymorphism of the CTLA-4 gene and systemic lupus erythematosus in Iranian patients. Int J Rheum Dis 2017; 20: 2040-4.
  • Online Mendelian Inheritance in Man. https://omim.org/. (Erişim Tarihi: 09.04.2020) .
  • National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/. (Erişim Tarihi: 09.04.2020)
  • NCBI-SNP. https://www.ncbi.nlm.nih.gov/snp/. (Erişim Tarihi: 09.04.2020)
  • Franz M, Rodriguez H, Lopes C, et al. GeneMANIA update 2018. Nucleic Acids Res 2018; 46: 60-4.
  • Mering VC, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 2003; 31: 258-61.
  • Mutarelli M, Marwah V, Rispoli R, et al. A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders. BMC Genomics 2014; 15: S5.
  • Sim LN, Kumar P, Hu J, Henikoff S, Schneider G, Pauline C. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res 2012: 40: 452-7.
  • Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013; 76: 7-20.
  • Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 2015; 28: 146-52.
  • Dweep H, Sticht C, Pandey P, Gretz N. miRWalk database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 2011; 44: 839-47.
  • Brunner MC, Chambers CA, Chan FK, Hanke J, Winoto A, Allison JP. CTLA-4-Mediated inhibition of early events of T cell proliferation. J Immunol 1999; 162: 5813-20.
  • Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016; 39: 98-106.
  • Piccirillo CA, Shevach EM. Naturally-occurring CD4 + CD25 + immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 2004; 16: 81-8.
  • Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25(+) CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000; 192: 303-9.
  • Chen K, Kolls JK. Interluekin-17A. Gene 2017; 30: 8-4.
  • Kim CH. FOXP3 and its role in the immune system. Adv Exp Med Biol 2009; 665: 17-9.
  • Ganesh BB, Bhattacharya A, Gopisetty A, Prabhakar BS. Role of cytokines in the pathogenesis and suppression of thyroid autoimmunity. J Interferon Cytokine Res 2011; 31: 721-31.
  • Hu Y, Zhang L, Chen H, et al. Analysis of regulatory T cell subsets and their expression of helios and PD-1 in patients with hashimoto thyroiditis. Int J Endocrinol 2019; 2019: 5368473.
  • Watanabe A, Inoue N, Watanabe M, et al. Increases of CD80 and CD86 Expression on peripheral blood cells and their gene polymorphisms in autoimmune thyroid disease. Immunol Invest 2020; 49: 191-203.
  • Caio RDC, Quaio Jozélio F, Carvalho Clovis A, Bueno CS Amanda S. Autoimmune disease and multiple autoantibodies in 42 patients with RA Sopathies. Am J Med Genet A 2012; 158A: 1077-82.
  • Li J, Zhou H. Fyn gene polymorphisms contribute to both trait and state anxieties in healthy Chinese-Han individuals. Psychiatr Genet 2012; 22: 312-3.
  • Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res 2016; 7: 68-74.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Research Articles [en] Araştırma Makaleleri [tr]
Yazarlar

Duygu KIRKIK> (Sorumlu Yazar)
University of Health Sciences
0000-0003-1417-6915
Türkiye


Sevgi KALKANLI Bu kişi benim
SAĞLIK BİLİMLERİ ÜNİVERSİTESİ
0000-0001-5288-6040
Türkiye


Eylem ÇAĞILTAY>
İSTANBUL SULTAN ABDÜLHAMİD HAN SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
0000-0003-3901-4015
Türkiye


Nevin KALKANLİ>
Özel DiyarLife Hastanesi
0000-0003-0635-2878
Türkiye

Yayımlanma Tarihi 21 Eylül 2020
Yayınlandığı Sayı Yıl 2020, Cilt 1, Sayı 3

Kaynak Göster

Bibtex @araştırma makalesi { jompac739257, journal = {Journal of Medicine and Palliative Care}, eissn = {2717-7505}, address = {Kırıkkale Üniversitesi Tıp Fakültesi, İç Hastalıkları Anabilim Dalı}, publisher = {MediHealth Academy Yayıncılık}, year = {2020}, volume = {1}, number = {3}, pages = {58 - 63}, doi = {10.47582/jompac.739257}, title = {Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi}, key = {cite}, author = {Kırkık, Duygu and Kalkanlı, Sevgi and Çağıltay, Eylem and Kalkanli, Nevin} }
APA Kırkık, D. , Kalkanlı, S. , Çağıltay, E. & Kalkanli, N. (2020). Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi . Journal of Medicine and Palliative Care , 1 (3) , 58-63 . DOI: 10.47582/jompac.739257
MLA Kırkık, D. , Kalkanlı, S. , Çağıltay, E. , Kalkanli, N. "Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi" . Journal of Medicine and Palliative Care 1 (2020 ): 58-63 <https://dergipark.org.tr/tr/pub/jompac/issue/56869/739257>
Chicago Kırkık, D. , Kalkanlı, S. , Çağıltay, E. , Kalkanli, N. "Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi". Journal of Medicine and Palliative Care 1 (2020 ): 58-63
RIS TY - JOUR T1 - Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi AU - DuyguKırkık, SevgiKalkanlı, EylemÇağıltay, NevinKalkanli Y1 - 2020 PY - 2020 N1 - doi: 10.47582/jompac.739257 DO - 10.47582/jompac.739257 T2 - Journal of Medicine and Palliative Care JF - Journal JO - JOR SP - 58 EP - 63 VL - 1 IS - 3 SN - -2717-7505 M3 - doi: 10.47582/jompac.739257 UR - https://doi.org/10.47582/jompac.739257 Y2 - 2020 ER -
EndNote %0 Journal of Medicine and Palliative Care Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi %A Duygu Kırkık , Sevgi Kalkanlı , Eylem Çağıltay , Nevin Kalkanli %T Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi %D 2020 %J Journal of Medicine and Palliative Care %P -2717-7505 %V 1 %N 3 %R doi: 10.47582/jompac.739257 %U 10.47582/jompac.739257
ISNAD Kırkık, Duygu , Kalkanlı, Sevgi , Çağıltay, Eylem , Kalkanli, Nevin . "Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi". Journal of Medicine and Palliative Care 1 / 3 (Eylül 2020): 58-63 . https://doi.org/10.47582/jompac.739257
AMA Kırkık D. , Kalkanlı S. , Çağıltay E. , Kalkanli N. Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi. J Med Palliat Care / JOMPAC / Jompac. 2020; 1(3): 58-63.
Vancouver Kırkık D. , Kalkanlı S. , Çağıltay E. , Kalkanli N. Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi. Journal of Medicine and Palliative Care. 2020; 1(3): 58-63.
IEEE D. Kırkık , S. Kalkanlı , E. Çağıltay ve N. Kalkanli , "Otoimmün tiroid hastalıklarında CTLA-4 geninin in silico analizinin değerlendirilmesi", Journal of Medicine and Palliative Care, c. 1, sayı. 3, ss. 58-63, Eyl. 2020, doi:10.47582/jompac.739257

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