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

Year 2020, Volume: 83 Issue: 2, 81 - 85, 23.03.2020

Abstract

Objective: Ankylosing spondylitis (AS) is a chronic inflammatory disorder. Micro RNAs (miRNAs) can function as either oncogenes or tumor suppressor genes. Altered miRNA expression has been implicated 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 78 AS patients and 79 healthy controls. miR-196a2T/C variant was genotyped by PCR-RFLP. Odds ratio (OR) with 95% confidence interval (95%CI) were calculated using the χ2 test. Results: The frequency of T/C and T/T genotypes of the miR196a2T/C were higher in AS patients compared to healthy controls (p=0.034 and p=0.028, respectively). The subjects carrying the miR-196a2T/C variant T/T genotype showed a 2.542-fold increased AS risk than the control group. However, no difference was observed in the allele frequencies of miR-196a2T/C between AS patients and the controls. It was found that C/C genotype of miR-196a2T/C variant was more frequent in AS patients with enthesitis than AS patients without enthesitis (p=0.042). Conclusion: The miR-196a2T/C variant represents a genetic risk factor for increased susceptibility to AS and is associated with enthesitis in the Turkish population.

References

  • 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.
  • 2. Wang Y, Yi XD, Lu HL. Influence of CYP2C9 and COX2 Genetic Polymorphisms on Clinical Efficacy of NonSteroidal Anti-Inflammatory Drugs in Treatment of Ankylosing Spondylitis. Med Sci Monit 2017;23:1775-82.
  • 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.
  • 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.
  • 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.
  • 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;438:67174.
  • 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.
  • 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.
  • 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.
  • 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.
  • 13. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell 2009;136:26-36.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 20. Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012;22:1243-54.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 miR499A>G polymorphisms with gastric cancer and survival in the Korean population. Mol Carcinog 2013;52(S1):E39-E51.
  • 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 miR499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler Thromb Vasc Biol 2013;33:42030.
  • 27. Jeon YJ, Kim SY, Rah H, Choi DH, Cha SH, Yoon TK, et al. Association of the miR-146aC>G, miR-149T>C, miR196a2T>C, and miR-499A>G polymorphisms with risk of spontaneously aborted fetuses. Am J Reprod Immunol 2012;68:408-17.
  • 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.

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

Year 2020, Volume: 83 Issue: 2, 81 - 85, 23.03.2020

Abstract

Amaç: Ankilozan spondilit (AS) kronik, enflamatuar bir hastalıktır. MikroRNA’lar (miRNAlar) onkogen veya tümör baskılayıcı genler olarak fonksiyon yapabilirler. Çeşitli hastalıkların patogenezinde miRNA ekspresyonunun 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.

References

  • 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.
  • 2. Wang Y, Yi XD, Lu HL. Influence of CYP2C9 and COX2 Genetic Polymorphisms on Clinical Efficacy of NonSteroidal Anti-Inflammatory Drugs in Treatment of Ankylosing Spondylitis. Med Sci Monit 2017;23:1775-82.
  • 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.
  • 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.
  • 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.
  • 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;438:67174.
  • 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.
  • 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.
  • 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.
  • 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.
  • 13. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell 2009;136:26-36.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 20. Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012;22:1243-54.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 miR499A>G polymorphisms with gastric cancer and survival in the Korean population. Mol Carcinog 2013;52(S1):E39-E51.
  • 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 miR499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler Thromb Vasc Biol 2013;33:42030.
  • 27. Jeon YJ, Kim SY, Rah H, Choi DH, Cha SH, Yoon TK, et al. Association of the miR-146aC>G, miR-149T>C, miR196a2T>C, and miR-499A>G polymorphisms with risk of spontaneously aborted fetuses. Am J Reprod Immunol 2012;68:408-17.
  • 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.
There are 28 citations in total.

Details

Primary Language English
Journal Section RESEARCH
Authors

Sacide Pehlivan 0000-0003-1272-5845

Savaş Gürsoy This is me 0000-0002-1673-9905

Ayşe Feyda Nursal This is me 0000-0001-7639-1122

Mazlum Serdar Akaltun This is me 0000-0002-9666-9483

Kürşat Özdilli This is me 0000-0002-7129-5024

Mustafa Pehlivan This is me 0000-0002-6692-085X

Publication Date March 23, 2020
Submission Date March 12, 2019
Published in Issue Year 2020 Volume: 83 Issue: 2

Cite

APA Pehlivan, S., Gürsoy, S., Nursal, A. F., Akaltun, M. S., et al. (2020). THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. Journal of Istanbul Faculty of Medicine, 83(2), 81-85.
AMA Pehlivan S, Gürsoy S, Nursal AF, Akaltun MS, Özdilli K, Pehlivan M. THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İst Tıp Fak Derg. March 2020;83(2):81-85.
Chicago Pehlivan, Sacide, Savaş Gürsoy, Ayşe Feyda Nursal, Mazlum Serdar Akaltun, Kürşat Özdilli, and Mustafa Pehlivan. “THE MiR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION”. Journal of Istanbul Faculty of Medicine 83, no. 2 (March 2020): 81-85.
EndNote Pehlivan S, Gürsoy S, Nursal AF, Akaltun MS, Özdilli K, Pehlivan M (March 1, 2020) THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. Journal of Istanbul Faculty of Medicine 83 2 81–85.
IEEE S. Pehlivan, S. Gürsoy, A. F. Nursal, M. S. Akaltun, K. Özdilli, and M. Pehlivan, “THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION”, İst Tıp Fak Derg, vol. 83, no. 2, pp. 81–85, 2020.
ISNAD Pehlivan, Sacide et al. “THE MiR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION”. Journal of Istanbul Faculty of Medicine 83/2 (March 2020), 81-85.
JAMA Pehlivan S, Gürsoy S, Nursal AF, Akaltun MS, Özdilli K, Pehlivan M. THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İst Tıp Fak Derg. 2020;83:81–85.
MLA Pehlivan, Sacide et al. “THE MiR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION”. Journal of Istanbul Faculty of Medicine, vol. 83, no. 2, 2020, pp. 81-85.
Vancouver Pehlivan S, Gürsoy S, Nursal AF, Akaltun MS, Özdilli K, Pehlivan M. THE miR-196a2T/C VARIANT AS A POSSIBLE PREDISPOSING FACTOR FOR ANKYLOSING SPONDYLITIS IN A TURKISH POPULATION. İst Tıp Fak Derg. 2020;83(2):81-5.

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