Investigation of rs531564 Polymorphism in the Primary MicroRNA-124 Gene in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: Association with Disease Susceptibility and Clinical Characteristics
-
Mehdi Hassani
,
Mohammad Dehani
,
Maryam Zare Rafie
,
Emran Esmaeilzadeh
,
Saeideh Davar
,
Bahram Pakzad
,
Meysam Mosallaei
,
Seyyed Mohamad Hoseini
,
Hadi Bayat
,
Mohsen Soosanabadi
Abstract
MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk.
In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method.
Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001).
Our findings propose a considerable association between rs531564 polymorphism in the pri-miR-124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.
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4. Kamen DL. Environmental influences on systemic lupus erythematosus expression. Rheum Dis Clin North Am. 2014;40(3):401-9.
5. Orozco G, Eyre S, Hinks A, Bowes J, Morgan AW, Wilson AG, et al. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus. Annals Rheumatic dis. 2011;70(3):463-8.
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7. Lettre G, Rioux JD. Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet. 2008;17(R2):116-21.
8. Kochi Y. Genetics of autoimmune diseases: perspectives from genome-wide association studies. Inter Immunol. 2016;28(4):155-61.
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11. Ehtesham N, Mosallaei M, Karimzadeh MR, Moradikazerouni H, Sharifi M. microRNAs: key modulators of disease-modifying therapies in multiple sclerosis: Pancreatic cancer is one of the lethal malignant tumours in the world. In this study, we investigated the CAR T-Cell therapy of pancreatic cancer. International reviews of immunology. 2020;39(6):264-79.
12. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016;17(10):1712.
13. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol. 2018;9(402):258-63.
14. Simonian M, Sharifi M, Nedaeinia R, Mosallaie M, Khosravi S, Avan A, et al. Evaluation of miR-21 inhibition and its impact on cancer susceptibility candidate 2 long noncoding RNA in colorectal cancer cell line. Adv bio Res. 2018;7:14(2):15-9.
15. Raisch J, Darfeuille-Michaud A, Nguyen HTT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19(20):2985-96.
16. Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q. Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets. Cancer Lett. 2018;428(41):90-103.
17. Moszyńska A, Gebert M, Collawn JF, Bartoszewski R. SNPs in microRNA target sites and their potential role in human disease. Open Biol. 2017;7(4):48-54.
18. Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 2009;27(5):363-91.
19. Ehtesham N, Alani B, Mortazavi D, Azhdari S, Kenarangi T, Esmaeilzadeh E, et al. Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis. Iran J Allergy, Asthma Immunol. 2021;20(2):178-87.
20. Ricaño-Ponce I, Zhernakova DV, Deelen P, Luo O, Li X, Isaacs A, et al. Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs. J Autoimmun. 2016;68(4):62-74.
21. Kim Y, Kang C, Min B, Yi G-S. Detection and analysis of disease-associated single nucleotide polymorphism influencing post-translational modification. BMC Med Genomics. 2015;8(2):S7-9.
22. Karimzadeh MR, Zarin M, Ehtesham N, Khosravi S, Soosanabadi M, Mosallaei M, et al. MicroRNA binding site polymorphism in inflammatory genes associated with colorectal cancer: literature review and bioinformatics analysis. Cancer Gene Therapy. 2020;27(10):739-53.
23. Simonian M, Mosallaei M, Khosravi S, Salehi R. rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population. J cancer Res Therapeutics. 2019;15(1):15-26.
24. Mosallaei M, Simonian M, Esmaeilzadeh E, Bagheri H, Miraghajani M, Salehi AR, et al. Single nucleotide polymorphism rs10889677 in miRNAs Let-7e and Let-7f binding site of IL23R gene is a strong colorectal cancer determinant: Report and meta-analysis. Cancer genetics. 2019;239:46-53.
25. Wang Y, Ru J, Jin T, Sun M, Jia L, Sun G. An Approach to Identify Individual Functional Single Nucleotide Polymorphisms and Isoform MicroRNAs. BioMed Res Interna. 2019;2019:6193673.
26. Qin Z, Wang P-Y, Su D-F, Liu X. miRNA-124 in immune system and immune disorders. FrontImmunol. 2016;7:406.
27. Han SM, Na HY, Ham O, Choi W, Sohn M, Ryu SH, et al. TCF4-targeting miR-124 is differentially expressed amongst dendritic cell subsets. Immune Network. 2016;16(1):61-9.
28. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis. Front Immunol. 2009;60(5):1294-304.
29. Nakamachi Y, Ohnuma K, Uto K, Noguchi Y, Saegusa J, Kawano S. MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats. Ann Rheumatic dis. 2016;75(3):601-8.
30. Chen J, Peng L, Zhao Z, Yang Q, Yin F, Liu M, et al. HDAC1 potentiates CD4+ T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus. Cell Immunol. 2021;362:104284.
31. Qi L, Hu Y, Zhan Y, Wang J, Wang B-B, Xia H-F, et al. A SNP site in pri-miR-124 changes mature miR-124 expression but no contribution to Alzheimer's disease in a Mongolian population. Neuroscience lett. 2012;515(1):1-6.
32. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Front Immunol. 2019;71(9):1400-12.
33. Qin Z, Wang P-Y, Su D-F, Liu X. miRNA-124 in Immune System and Immune Disorders. Front Immunol. 2016;7:406.
34. Koukos G, Polytarchou C, Kaplan JL, Morley–Fletcher A, Gras–Miralles B, Kokkotou E, et al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology. 2013;145(4):842-52.
35. Zhou Q, Long L, Shi G, Zhang J, Wu T, Zhou B. Research of the methylation status of miR-124a gene promoter among rheumatoid arthritis patients. Clin Develop Immunol. 2013;2013:524204.
36. Zhang L, Zhang X, Si F. MicroRNA-124 represents a novel diagnostic marker in human lupus nephritis and plays an inhibitory effect on the growth and inflammation of renal mesangial cells by targeting TRAF6. Int J Clin Exp Pathol. 2019;12(5):1578-88.
37. Jin F, Hu H, Xu M, Zhan S, Wang Y, Zhang H, et al. Serum microRNA profiles serve as novel biomarkers for autoimmune diseases. Front Immunol. 2018;9:2381.
38. Sjöwall C, Zickert A, Skogh T, Wetterö J, Gunnarsson I. Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis. Arthritis Research & Therapy. 2009;11(6):R188.
39. Narayanan K, Marwaha V, Shanmuganandan K, Shankar S. Correlation between Systemic Lupus Erythematosus Disease Activity Index, C3, C4 and Anti-dsDNA Antibodies. Med J Armed Forces India. 2010;66(2):102-7.
40. Li Y, Zhang Y, Li X, Shi L, Tao W, Shi L, et al. Association study of polymorphisms in miRNAs with T2DM in Chinese population. I Int J Med Sci. 2015;12(11):875-80.
41. Gao X-r, Wang H-p, Zhang S-l, Wang M-x, Zhu Z-s. Pri-miR-124 rs531564 polymorphism and colorectal cancer risk. Sci Rep. 2015;5(1):1-7.
42. Ciccacci C, Politi C, Biancone L, Latini A, Novelli G, Calabrese E, et al. Polymorphisms in MIR122, MIR196A2, and MIR124A Genes are Associated with Clinical Phenotypes in Inflammatory Bowel Diseases. Mol Diagn Ther. 2017;21(1):107-14.
43. Chuanyin L, Xiaona W, Zhiling Y, Yu Z, Shuyuan L, Jie Y, et al. The association between polymorphisms in microRNA genes and cervical cancer in a Chinese Han population. Oncotarget. 2017;8(50):87914-9.
44. Danesh H, Hashemi M, Bizhani F, Hashemi SM, Bahari G. Association study of miR-100, miR-124-1, miR-218-2, miR-301b, miR-605, and miR-4293 polymorphisms and the risk of breast cancer in a sample of Iranian population. Gene. 2018;647(11):73-8.
45. Moazeni-Roodi A, Hashemi M. Association between miR-124-1 rs531564 polymorphism and risk of cancer: An updated meta-analysis of case-control studies. EXCLI journal. 2018;17:608-19.
2. Signorini V, Elefante E, Zucchi D, Trentin F, Bortoluzzi A, Tani C. One year in review 2020: systemic lupus erythematosus. Clin Exp Rheumatol. 2020;38(0):592-601.
3. Kim J-W, Suh C-H. Systemic Manifestations and Complications in Patients with Rheumatoid Arthritis. J Clin Med. 2020;9(6):2008-14.
4. Kamen DL. Environmental influences on systemic lupus erythematosus expression. Rheum Dis Clin North Am. 2014;40(3):401-9.
5. Orozco G, Eyre S, Hinks A, Bowes J, Morgan AW, Wilson AG, et al. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus. Annals Rheumatic dis. 2011;70(3):463-8.
6. Ceccarelli F, Agmon-Levin N, Perricone C. Genetic Factors of Autoimmune Diseases. J Immunol Res. 2016;2016:3476023.
7. Lettre G, Rioux JD. Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet. 2008;17(R2):116-21.
8. Kochi Y. Genetics of autoimmune diseases: perspectives from genome-wide association studies. Inter Immunol. 2016;28(4):155-61.
9. Moran-Moguel MC, Petarra-del Rio S, Mayorquin-Galvan EE, Zavala-Cerna MG. Rheumatoid Arthritis and miRNAs: A Critical Review through a Functional View. J Immunol Res. 2018;2018:2474529.
10. Mazzone R, Zwergel C, Artico M, Taurone S, Ralli M, Greco A, et al. The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics. 2019;11(1):34-9.
11. Ehtesham N, Mosallaei M, Karimzadeh MR, Moradikazerouni H, Sharifi M. microRNAs: key modulators of disease-modifying therapies in multiple sclerosis: Pancreatic cancer is one of the lethal malignant tumours in the world. In this study, we investigated the CAR T-Cell therapy of pancreatic cancer. International reviews of immunology. 2020;39(6):264-79.
12. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016;17(10):1712.
13. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol. 2018;9(402):258-63.
14. Simonian M, Sharifi M, Nedaeinia R, Mosallaie M, Khosravi S, Avan A, et al. Evaluation of miR-21 inhibition and its impact on cancer susceptibility candidate 2 long noncoding RNA in colorectal cancer cell line. Adv bio Res. 2018;7:14(2):15-9.
15. Raisch J, Darfeuille-Michaud A, Nguyen HTT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19(20):2985-96.
16. Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q. Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets. Cancer Lett. 2018;428(41):90-103.
17. Moszyńska A, Gebert M, Collawn JF, Bartoszewski R. SNPs in microRNA target sites and their potential role in human disease. Open Biol. 2017;7(4):48-54.
18. Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 2009;27(5):363-91.
19. Ehtesham N, Alani B, Mortazavi D, Azhdari S, Kenarangi T, Esmaeilzadeh E, et al. Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis. Iran J Allergy, Asthma Immunol. 2021;20(2):178-87.
20. Ricaño-Ponce I, Zhernakova DV, Deelen P, Luo O, Li X, Isaacs A, et al. Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs. J Autoimmun. 2016;68(4):62-74.
21. Kim Y, Kang C, Min B, Yi G-S. Detection and analysis of disease-associated single nucleotide polymorphism influencing post-translational modification. BMC Med Genomics. 2015;8(2):S7-9.
22. Karimzadeh MR, Zarin M, Ehtesham N, Khosravi S, Soosanabadi M, Mosallaei M, et al. MicroRNA binding site polymorphism in inflammatory genes associated with colorectal cancer: literature review and bioinformatics analysis. Cancer Gene Therapy. 2020;27(10):739-53.
23. Simonian M, Mosallaei M, Khosravi S, Salehi R. rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population. J cancer Res Therapeutics. 2019;15(1):15-26.
24. Mosallaei M, Simonian M, Esmaeilzadeh E, Bagheri H, Miraghajani M, Salehi AR, et al. Single nucleotide polymorphism rs10889677 in miRNAs Let-7e and Let-7f binding site of IL23R gene is a strong colorectal cancer determinant: Report and meta-analysis. Cancer genetics. 2019;239:46-53.
25. Wang Y, Ru J, Jin T, Sun M, Jia L, Sun G. An Approach to Identify Individual Functional Single Nucleotide Polymorphisms and Isoform MicroRNAs. BioMed Res Interna. 2019;2019:6193673.
26. Qin Z, Wang P-Y, Su D-F, Liu X. miRNA-124 in immune system and immune disorders. FrontImmunol. 2016;7:406.
27. Han SM, Na HY, Ham O, Choi W, Sohn M, Ryu SH, et al. TCF4-targeting miR-124 is differentially expressed amongst dendritic cell subsets. Immune Network. 2016;16(1):61-9.
28. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis. Front Immunol. 2009;60(5):1294-304.
29. Nakamachi Y, Ohnuma K, Uto K, Noguchi Y, Saegusa J, Kawano S. MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats. Ann Rheumatic dis. 2016;75(3):601-8.
30. Chen J, Peng L, Zhao Z, Yang Q, Yin F, Liu M, et al. HDAC1 potentiates CD4+ T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus. Cell Immunol. 2021;362:104284.
31. Qi L, Hu Y, Zhan Y, Wang J, Wang B-B, Xia H-F, et al. A SNP site in pri-miR-124 changes mature miR-124 expression but no contribution to Alzheimer's disease in a Mongolian population. Neuroscience lett. 2012;515(1):1-6.
32. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Front Immunol. 2019;71(9):1400-12.
33. Qin Z, Wang P-Y, Su D-F, Liu X. miRNA-124 in Immune System and Immune Disorders. Front Immunol. 2016;7:406.
34. Koukos G, Polytarchou C, Kaplan JL, Morley–Fletcher A, Gras–Miralles B, Kokkotou E, et al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology. 2013;145(4):842-52.
35. Zhou Q, Long L, Shi G, Zhang J, Wu T, Zhou B. Research of the methylation status of miR-124a gene promoter among rheumatoid arthritis patients. Clin Develop Immunol. 2013;2013:524204.
36. Zhang L, Zhang X, Si F. MicroRNA-124 represents a novel diagnostic marker in human lupus nephritis and plays an inhibitory effect on the growth and inflammation of renal mesangial cells by targeting TRAF6. Int J Clin Exp Pathol. 2019;12(5):1578-88.
37. Jin F, Hu H, Xu M, Zhan S, Wang Y, Zhang H, et al. Serum microRNA profiles serve as novel biomarkers for autoimmune diseases. Front Immunol. 2018;9:2381.
38. Sjöwall C, Zickert A, Skogh T, Wetterö J, Gunnarsson I. Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis. Arthritis Research & Therapy. 2009;11(6):R188.
39. Narayanan K, Marwaha V, Shanmuganandan K, Shankar S. Correlation between Systemic Lupus Erythematosus Disease Activity Index, C3, C4 and Anti-dsDNA Antibodies. Med J Armed Forces India. 2010;66(2):102-7.
40. Li Y, Zhang Y, Li X, Shi L, Tao W, Shi L, et al. Association study of polymorphisms in miRNAs with T2DM in Chinese population. I Int J Med Sci. 2015;12(11):875-80.
41. Gao X-r, Wang H-p, Zhang S-l, Wang M-x, Zhu Z-s. Pri-miR-124 rs531564 polymorphism and colorectal cancer risk. Sci Rep. 2015;5(1):1-7.
42. Ciccacci C, Politi C, Biancone L, Latini A, Novelli G, Calabrese E, et al. Polymorphisms in MIR122, MIR196A2, and MIR124A Genes are Associated with Clinical Phenotypes in Inflammatory Bowel Diseases. Mol Diagn Ther. 2017;21(1):107-14.
43. Chuanyin L, Xiaona W, Zhiling Y, Yu Z, Shuyuan L, Jie Y, et al. The association between polymorphisms in microRNA genes and cervical cancer in a Chinese Han population. Oncotarget. 2017;8(50):87914-9.
44. Danesh H, Hashemi M, Bizhani F, Hashemi SM, Bahari G. Association study of miR-100, miR-124-1, miR-218-2, miR-301b, miR-605, and miR-4293 polymorphisms and the risk of breast cancer in a sample of Iranian population. Gene. 2018;647(11):73-8.
45. Moazeni-Roodi A, Hashemi M. Association between miR-124-1 rs531564 polymorphism and risk of cancer: An updated meta-analysis of case-control studies. EXCLI journal. 2018;17:608-19.
| Files | ||
| Issue | Vol 20 No 3 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i3.6336 | |
| Keywords | ||
| Rheumatoid arthritis Single nucleotide polymorphism. Systemic lupus erythematosus | ||
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How to Cite
1.
Hassani M, Dehani M, Zare Rafie M, Esmaeilzadeh E, Davar S, Pakzad B, Mosallaei M, Hoseini SM, Bayat H, Soosanabadi M. Investigation of rs531564 Polymorphism in the Primary MicroRNA-124 Gene in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: Association with Disease Susceptibility and Clinical Characteristics. Iran J Allergy Asthma Immunol. 2021;20(3):303-313.
