Yıl: 2020 Cilt: 83 Sayı: 2 Sayfa Aralığı: 81 - 85 Metin Dili: İngilizce DOI: 10.26650/IUITFD.2019.0023 İndeks Tarihi: 27-04-2020

THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION

Öz:
Objective: Ankylosing spondylitis (AS) is a chronic inflammatorydisorder. MicroRNAs (miRNAs) can function as either oncogenesor tumor suppressor genes. Altered miRNA expression has beenimplicated in the pathogenesis of several diseases. Therefore,we aimed to explore the effects of miR-196a2T/C (rs11614913)variant profile on susceptibility to AS in a Turkish population.Materials and Methods: Blood samples were collected from 78AS patients and 79 healthy controls. miR-196a2T/C variant wasgenotyped by PCR-RFLP. Odds ratio (OR) with 95% confidenceinterval (95%CI) were calculated using the χ2 test.Results: The frequency of T/C and T/T genotypes of the miR-196a2T/C were higher in AS patients compared to healthy controls(p=0.034 and p=0.028, respectively). The subjects carryingthe miR-196a2T/C variant T/T genotype showed a 2.542-foldincreased AS risk than the control group. However, no differencewas observed in the allele frequencies of miR-196a2T/Cbetween AS patients and the controls. It was found that C/Cgenotype of miR-196a2T/C variant was more frequent in ASpatients with enthesitis than AS patients without enthesitis(p=0.042). factor for increased susceptibility to AS and is associated withenthesitis in the Turkish population.
Anahtar Kelime:

TÜRK POPÜLASYONUNDA ANKİLOZAN SPONDİLİTE YATKINLIK SAĞLAYICI FAKTÖR OLARAK miR-196a2T/C VARYANTI

Öz:
Amaç: Ankilozan spondilit (AS) kronik, enflamatuar bir hastalıktır. MikroRNA’lar (miRNA’,lar) onkogen veya tümör baskılayıcı genler olarak fonksiyon yapabilirler. Çeşitli hastalıkların patogenezinde miRNA ekspresyonu’nun değişmesi bulunmaktadır. Bu nedenle, Türk toplumunda AS yatkınlığında miR-196a2T/C (rs11614913) varyant profilinin etkilerini araştırmayı amaçladık. Gereç ve Yöntem: 78 AS hastası ve 79 kontrolden kan örnekleri toplandı. miR-196a2T/C varyantı PCR-RFLP ile genotiplendi. χ2 testi kullanılarak %95 güven aralığı ile Odds oranı (OR) hesaplandı. Bulgular: miR-196a2T/C T/C ve T/T genotipleri AS hastalarında sağlıklı kontrollere kıyasla daha yüksekti (sırasıyla, p=0.034 and p=0.028). miR-196a2T/C varyant T/T genotipini taşıyan kişiler kontrol grubundan 2,542 kat artmış AS riski gösterdiler. Ancak, miR-196a2T/C allele frekansları açısından AS hastaları ve kontroller arasında fark saptanmadı. miR-196a2T/C varyant C/C genotipinin entezitli AS hastalarında entezit bulunmayan AS hastalarından daha çok olduğu bulundu (p=0.042). Sonuç: miR-196a2T/C varyantı Türk toplumunda AS ve hastalığın entezit ile ilişkisine yatkınlık sağlayan genetik risk faktörü rolü göstermektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Han R, Xia Q, Xu S, Fan D, Pan F. Interleukin-23 receptor polymorphism (rs10889677 A/C) in ankylosing spondylitis: Meta-analysis in Caucasian and Asian populations. Clin Chim Acta 2018;477:53-9. [CrossRef]
  • 2. Wang Y, Yi XD, Lu HL. Influence of CYP2C9 and COX-2 Genetic Polymorphisms on Clinical Efficacy of Non- Steroidal Anti-Inflammatory Drugs in Treatment of Ankylosing Spondylitis. Med Sci Monit 2017;23:1775-82. [CrossRef]
  • 3. Niu Z, Wang J, Zou H, Yang C, Huang W, Jin L. Common MIR146A Polymorphisms in Chinese Ankylosing Spondylitis Subjects and Controls. PLoS One 2015;10:e0137770. [CrossRef]
  • 4. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008;9:102-14.
  • 5. Lu J, Getz G, Miska EA, Alvarez-Salveda E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435:834-38. [CrossRef]
  • 6. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 2010;10:111-22. [CrossRef]
  • 7. Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature 2005;438:671- 74. [CrossRef]
  • 8. Lim JJ, Shin DA, Jeon YJ, Kumar H, Sohn S, Min HS, et al. Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with Ossification of the Posterior Longitudinal Ligament of the Cervical Spine. PLoS One 2016;11:e0159756. [CrossRef]
  • 9. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8. [CrossRef]
  • 10. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215. [CrossRef]
  • 11. Bodal VK, Sangwan S, Bal MS, Kaur M, Sharma S, Kaur B. Association between Microrna 146a and Microrna 196a2 Genes Polymorphism and Breast Cancer Risk in North Indian Women. Asian Pac J Cancer Prev 2017;18:2345-8.
  • 12. Smith JA. Update on ankylosing spondylitis: current concepts in pathogenesis.Curr Allergy Asthma Rep 2015;15:489. [CrossRef]
  • 13. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell 2009;136:26-36. [CrossRef]
  • 14. Hackl M, Heilmeier U, Weilner S, Grillari J. Circulating microRNAs as novel biomarkers for bone diseases - Complex signatures for multifactorial diseases? Mol Cell Endocrinol 2016;432:83-95. [CrossRef]
  • 15. Arfat Y, Xiao WZ, Ahmad M, Zhao F, Li DJ, Sun YL, et al. Role of microRNAs in osteoblasts differentiation and bone disorders. Curr Med Chem 2015;22:748-58. [CrossRef]
  • 16. Xu HY, Wang ZY, Chen JF, Wang TY, Wang LL, Tang LL, et al. Association between Ankylosing Spondylitis and the miR-146a and miR-499 Polymorphisms. PLoS One 2015;10:e0122055. [CrossRef]
  • 17. Yang L, Du L, Yue Y, Huang Y, Zhou Q, Cao S, et al. miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis. Invest Ophthalmol Vis Sci 2017;58:1991-2001. [CrossRef]
  • 18. Qian BP, Ji ML, Qiu Y, Wang B, Yu Y, Shi W, et al. Identification of Serum miR-146a and miR-155 as Novel Noninvasive Complementary Biomarkers for Ankylosing Spondylitis. Spine (Phila Pa 1976) 2016;41:735-42. [CrossRef]
  • 19. Duan S, Mi S, Zhang W, Dolan ME. Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes. RNA Biol 2009;6:412-25. [CrossRef]
  • 20. Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012;22:1243-54. [CrossRef]
  • 21. Park R, Lee WJ, Ji JD. Association between the three functional miR-146a single-nucleotide polymorphisms, rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis. Autoimmunity 2016;49:451-8. [CrossRef]
  • 22. Fattah SA, Ghattas MH, Saleh SM, Abo-Elmatty DM. Premicro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population.Indian J Clin Biochem 2018;33:96-101. [CrossRef]
  • 23. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 2008;118:2600-8. [CrossRef]
  • 24. Vinci S, Gelmini S, Pratesi N, Conti S, Malentacchi F, Simi L, et al. Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med 2011;49:2073-80. [CrossRef]
  • 25. Ahn DH, Rah H, Choi YK, Jeon YJ, Min KT, Kwack K, et al. Association of the miR-146aC>G, miR-196a2C>T, and miR- 499A>G polymorphisms with gastric cancer and survival in the Korean population. Mol Carcinog 2013;52(S1):E39-E51. [CrossRef]
  • 26. Jeon YJ, Kim OJ, Kim SY, Oh SH, Oh D, Kim OJ, et al. Association of the miR-146a, miR-149, miR-196a2, and miR- 499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler Thromb Vasc Biol 2013;33:420- 30. [CrossRef]
  • 27. Jeon YJ, Kim SY, Rah H, Choi DH, Cha SH, Yoon TK, et al. Association of the miR-146aC>G, miR-149T>C, miR- 196a2T>C, and miR-499A>G polymorphisms with risk of spontaneously aborted fetuses. Am J Reprod Immunol 2012;68:408-17. [CrossRef]
  • 28. Qi J, Hou S, Zhang Q, Liao D, Wei L, Fang J, et al. A functional variant of pre-miRNA-196a2 confers risk for Behcet’s disease but not for Vogt-Koyanagi-Harada syndrome or AAU in ankylosing spondylitis. Hum Genet 2013;132:1395-404. [CrossRef]
APA pehlivan s, Gursoy S, Nursal A, Akaltun M, OZDILLI K, PEHLİVAN M (2020). THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. , 81 - 85. 10.26650/IUITFD.2019.0023
Chicago pehlivan sacide,Gursoy Savas,Nursal Ayse Feyda,Akaltun Mazlum Serdar,OZDILLI KÜRSAT,PEHLİVAN MUSTAFA THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. (2020): 81 - 85. 10.26650/IUITFD.2019.0023
MLA pehlivan sacide,Gursoy Savas,Nursal Ayse Feyda,Akaltun Mazlum Serdar,OZDILLI KÜRSAT,PEHLİVAN MUSTAFA THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. , 2020, ss.81 - 85. 10.26650/IUITFD.2019.0023
AMA pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. . 2020; 81 - 85. 10.26650/IUITFD.2019.0023
Vancouver pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. . 2020; 81 - 85. 10.26650/IUITFD.2019.0023
IEEE pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M "THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION." , ss.81 - 85, 2020. 10.26650/IUITFD.2019.0023
ISNAD pehlivan, sacide vd. "THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION". (2020), 81-85. https://doi.org/10.26650/IUITFD.2019.0023
APA pehlivan s, Gursoy S, Nursal A, Akaltun M, OZDILLI K, PEHLİVAN M (2020). THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İstanbul Tıp Fakültesi Dergisi, 83(2), 81 - 85. 10.26650/IUITFD.2019.0023
Chicago pehlivan sacide,Gursoy Savas,Nursal Ayse Feyda,Akaltun Mazlum Serdar,OZDILLI KÜRSAT,PEHLİVAN MUSTAFA THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İstanbul Tıp Fakültesi Dergisi 83, no.2 (2020): 81 - 85. 10.26650/IUITFD.2019.0023
MLA pehlivan sacide,Gursoy Savas,Nursal Ayse Feyda,Akaltun Mazlum Serdar,OZDILLI KÜRSAT,PEHLİVAN MUSTAFA THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İstanbul Tıp Fakültesi Dergisi, vol.83, no.2, 2020, ss.81 - 85. 10.26650/IUITFD.2019.0023
AMA pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İstanbul Tıp Fakültesi Dergisi. 2020; 83(2): 81 - 85. 10.26650/IUITFD.2019.0023
Vancouver pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İstanbul Tıp Fakültesi Dergisi. 2020; 83(2): 81 - 85. 10.26650/IUITFD.2019.0023
IEEE pehlivan s,Gursoy S,Nursal A,Akaltun M,OZDILLI K,PEHLİVAN M "THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION." İstanbul Tıp Fakültesi Dergisi, 83, ss.81 - 85, 2020. 10.26650/IUITFD.2019.0023
ISNAD pehlivan, sacide vd. "THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION". İstanbul Tıp Fakültesi Dergisi 83/2 (2020), 81-85. https://doi.org/10.26650/IUITFD.2019.0023