Genetic Variation in Intergenic and Exonic miRNA Sequence and Risk of Multiple Sclerosis in the Isfahan Patients
,
Abstract
MicroRNAs (miRNAs), have been documented to perform a key role in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory and autoimmune disease. Recent studies have shown that single nucleotide polymorphism in the sequence of the miRNA may change their production and expression which can lead to miRNA dysfunction and pathogenicity. Some studies have reported the relationship between miRNA polymorphism and the increased risk of autoimmune disease. This study was conducted to investigate the association between mir155 rs767649, mir196a2 rs11614913 and mir23a rs3745453 polymorphism and the risk of multiple sclerosis in the Iranian MS patients in Isfahan. A population of 80 patients and the same number control were selected. After DNA extraction, genotyping was performed through tetra amplification refractory mutation system-PCR method (T ARMS PCR). The frequencies of TT, TC and CC genotypes of mir23a were 46, 35 and 20% in MS patients and 42, 14 and 24 in healthy subjects respectively. These results showed that individuals carrying the genotypes of rs3745453 TC had a 2.3-fold increased risk of MS (OR=2.3, p=0.048). There was no significant difference between genotypes and allele frequency of mir155 and mir196a2 in patients and healthy controls (p>0.05). Our findings specified that CT heterozygosity in mir23a gene significantly related with risk of MS. Unlike mir155 and mir196a2, mir23a rs3745453 may have contributed to the etiology of MS in Isfahan patients. However, extensive studies are required to gain more reliable and authentic results.
1. Etemadifar M, Sajjadi S, Nasr Z, Firoozeei TS, Abtahi SH, Akbari M, et al. Epidemiology of multiple sclerosis in Iran: a systematic review. Eur Neurol 2013;70(5-6):356-63.
2. Confavreux C, Vukusic S. The natural history of multiple sclerosis. Rev Prat 2013; 56(12): 1313-1320.
3. Gourraud PA, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: an up-to-date review. Immunological reviews 2012; 248(1):87- 103.
4. Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol 2012; 13: 249-58.
5. Wu C, Li M, Hu C, Duan H. Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy. Cancer Chemother Pharmacol 2014;73:335–41.
6. Yu H, Jiang L, Sun C, Guo L, Lin M, Huang J, et al. Decreased circulating mir-375: a potential biomarker for patients with non-small-cell lung cancer. Gene 2013; 24:01419–24.
7. Haghikia A, Haghikia A, Hellwig K, Barani skin A, Holzmann A, Décard B F, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: A case-control study. Neurology 2012; 79: 2166–2170.
8. Ajit S K. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors 2012; 12 , 3359–3369.
9. Martinelli-Boneschi F, Fenoglio C, Brambilla P, Sorosina M, Giacalone G, Esposito F, et al. MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers. Neurosci Lett 2012; 508, 4–8 .
10. Lv Y, Qi R, Xu J, Di Z, Zheng H, Huo W, et al. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS ONE 2014; 9: e115448- 17.
11. Zhu J, Huang X, Su G, Wang L, Wu F, Zhang T, et al. High expression levels of microRNA-629, microRNA-525-5p, and microRNA-516a-3p in paediatric systemic lupus erythematosus. Clin. Rheumatol 2014;33: 807–815.
12. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009; 132: 3342– 3352.
13. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference-based therapeutics. Nature 2009; 457:426–433.
14. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 2009; 32:189–194.
15. Ridolfi E, Fenoglio C, Cantoni C, Calvi A, De Riz M, Pietroboni A, et al. Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis. Int J Mol Sci 2013; 14(3):4375-84.
16. Zhang XW, Liu N, Chen S, Wang Y, Zhang ZX, Sun YY, et al. High microRNA-23a expression in laryngeal squamous cell carcinoma is associated with poor patient prognosis. Diagn Pathol 2015; 3:1-7 .
17 Yang Z, Chen H, Si H, Li X, Ding X, Sheng Q, et al. Serum mir-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetol 2014; 51(5):823-31.
18. Xiong W, Lin Y, Xu L, Tamadon A, Zou S, Tian F, et al. Circulatory microRNA 23a and microRNA 23b and polycystic ovary syndrome (PCOS): the effects of body mass index and sex hormones in an Eastern Han Chinese population. J Ovarian Res 2017; 1310(1):1-11.
19. Wang Y, Zhang ZX, Chen S, Qiu GB, Xu ZM, Fu WN. Methylation Status of SP1 Sites within mir-23a-27a-24-2 Promoter Region Influences Laryngeal Cancer Cell Proliferation and Apoptosis. Biomed Res Int 2016; 1-8.
20. Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA 2007; 104:19971–19976.
21. Palmieri A, Pezzetti F, Avantaggiato A, Lo Muzio L, Scarano A, Rubini C, et al. Titanium acts on osteoblast translational process. J Oral Implantol 2008; 34:190–195.
22. Saumet A, Vetter G, Bouttier M, Portales-Casamar E, Wasserman WW, Maurin T, et al. Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia. Blood 2009; 113:412-421.
23. Assmann TS, Duarte GC, Brondani LA, de Freitas PH, Martins ÉM, Canani LH, et al. Polymorphisms in genes encoding mir-155 and mir-146a are associated with protection to type 1 diabetes mellitus. Acta Diabetol 2017; 54(5):433-441.
24. Wang S, Cao X, Ding B, Chen J, Cui M, Xu Y, et al. The rs767649 polymorphism in the promoter of mir-155 contributes to the decreased risk for cervical cancer in a Chinese population. Gene 2016; 595(1):109-114.
25. Zhengrong Y, Xu Zeng D Y, Weilu W, Zhihua L. Effects of Common Polymorphism rs11614913 in Hsa-mir-196a2 on Lung Cancer Risk.plos one 2013; 8(4):1-8.
26. Xie K, Ma H, Liang C, Wang Ch, Qin N, Shen W, et al. A functional variant in mir- 155 regulation region contributes to lung cancer risk and survival. Onco target 2015; 6(40):42781–42792.
27. Ni Q, Ji A, Yin J, Wang X and Liu X. Effects of Two Common Polymorphisms rs2910164 in mir-146a and rs11614913 in mir-196a2 on Gastric Cancer Susceptibility. Gastroenterol Res and Pract 2015; 1-10.
28. Han BW, Li ZH, Liu SF, Han HB, Dong SJ, Zou HJ, et l. A comprehensive review of microRNA-related polymorphisms in gastric cancer. Genet Mol Res 2016 ;15(2).
29.Kiselev I, Bashinskaya V , Kulakova O, Baulina N, Popova E, Boyko A, et al. Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity. Int J Mol Sci 2015; 16: 20067-20081.
| Files | ||
| Issue | Vol 17, No 5 (2018) | |
| Section | Brief Communication | |
| DOI | https://doi.org/10.18502/ijaai.v17i5.305 | |
| Keywords | ||
| Genetic variation MiRNA Multiple sclerosis T ARMS PCR | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
