Document Type : Original articles

Authors

1 Department of Microbiology, College of Medicine, University of Anbar, Anbar, Iraq

2 Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Iraq

Abstract

Background: Micro RNA155 (miR-155) was identified as an essential determinant in immunological responses, and its genetic variants have increasing attention due to their ability to modulate its expression and potentially influence the susceptibility to autoimmune illnesses including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, etc.
Objectives: To examine the impact of miR-155 gene polymorphism (rs767649A>T) and miR-155 gene expression and their association with multiple sclerosis (MS) in a sample of Iraqi patients.
Materials and Methods: A total of 75 blood specimens were obtained from individuals diagnosed with MS. While an additional 75 blood specimens were collected from evidently healthy participants serving as a control group, with an age ranged 20-71 years. miR-155 gene polymorphism (rs767649 A>T) was determined utilizing Tetra-ARMS Polymerase Chain Reaction (Tetra-ARMS PCR) and miR-155 expression was evaluated using Real-time Polymerase Chain Reaction (RT-PCR).
Results: The females experienced MS at a higher rate (69.33%) compared to the males. Furthermore, the age group 30-39 years showed a greater susceptibility to the disease (54.67%). The analysis of miR-155 (rs767649 A>T) SNP in MS patients indicated that 7 (9.34%) had the wild genotype (AA(, 31 (41.33%) had the heterogeneous genotype )AT(, and 37 (49.33%) had the mutant genotype )TT(. These differences were statistically significant (P-value = 0.040). A allele frequency was 45 (0.3) (OR: 0.25; CI: 0.15-0.41) and T allele frequency was 105 (0.7) (OR: 3.91; CI: 2.42-6.33) in MS patients. While analysis of miR-155 gene expression demonstrated a significant increase in the patient group (1.82 ± 0.25 fold) compared to the healthy control group (0.33 ± 0.13 fold). The relationship between miR-155 gene expression and miR-155 genotypes in MS patients, revealed a notable elevation in miR-155 gene expression at the TT genotype (3.15 ± 0.73 fold), followed by TA genotype (1.29 ±0.65fold) and finally AA genotype (0.37 ± 0.19 fold) with highly statistically significant difference (P-value =  0.001).
Conclusion: There was a significant positive correlation between miR-155 (rs767649 A>T) genotypes and miR-155 expression and susceptibility to MS in Iraqi patients. These findings suggests that miR-155 may hold potential as a diagnostic and therapeutic marker for the disease.

Keywords

Main Subjects

[1]      A. Al-Araji and A. I. Mohammed, “Multiple sclerosis in Iraq: does it have the same features encountered in Western countries?,” J. Neurol. Sci., vol. 234, no. 1–2, pp. 67–71, 2005.
[2]      M. F. Jalal, A. O. Hatem, and E. S. Al-Obeidy, “Human leukocyte antigen (HLA) typing in Iraqi patient with multiple sclerosis (MS),” in MULTIPLE SCLEROSIS JOURNAL, vol. 24, no. 2, pp. NP26–NP27, 2018.
[3]      C. E. Condrat et al., “miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis,” Cells, vol. 9, no. 2, p. 276, 2020.
[4]      J. A. Slota and S. A. Booth, “MicroRNAs in neuroinflammation: implications in disease pathogenesis, biomarker discovery and therapeutic applications,” Non-coding RNA, vol. 5, no. 2, p. 35, 2019.
[5]      C. E. McCoy, “miR-155 dysregulation and therapeutic intervention in multiple sclerosis,” Regul. Inflamm. Signal. Heal. Dis., pp. 111–131, 2017.
[6]      T. S. Assmann et al., “Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus,” Acta Diabetol., vol. 54, pp. 433–441, 2017.
[7]      S. Pashangzadeh, M. Motallebnezhad, F. Vafashoar, A. Khalvandi, and N. Mojtabavi, “Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases,” Front. Immunol., vol. 12, p. 669382, 2021.
[8]      Z. Golshani, Z. Hojati, A. Sharifzadeh, V. Shaygannejad, and M. Jafarinia, “Genetic variation in intergenic and exonic miRNA sequence and risk of multiple sclerosis in the isfahan patients,” Iran. J. Allergy, Asthma Immunol., pp. 477–484, 2018.
[9]      L. Zheng et al., “Lanthanum chloride causes neurotoxicity in rats by upregulating miR-124 expression and targeting PIK3CA to regulate the PI3K/Akt signaling pathway,” Biomed Res. Int., vol. 2020, 2020.
[10]    A. Zenere et al., “Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls,” J. Neuroinflammation, vol. 20, no. 1, pp. 1–20, 2023.
[11]    H. K. Hassoun et al., “Expert opinion on the pharmacological management of multiple sclerosis in women of childbearing age in Iraq,” Heliyon, 2023.
[12]    K. Borziak and J. Finkelstein, “X-linked genetic risk factors that promote autoimmunity and dampen remyelination are associated with multiple sclerosis susceptibility,” Mult. Scler. Relat. Disord., vol. 66, p. 104065, 2022.
[13]    H. A. Al-Hamadani, “The Role of Gender in Early Onset Relapsing Remitting Multiple Sclerosis,” Iraqi Postgrad. Med. J., vol. 14, no. 2, 2015.
[14]    H. K. Hassoun, A. Al-Mahadawi, N. M. Sheaheed, S. M. Sami, A. Jamal, and Z. Allebban, “Epidemiology of multiple sclerosis in Iraq: retrospective review of 4355 cases and literature review,” Neurol. Res., vol. 44, no. 1, pp. 14–23, 2022.
[15]    F. S. Hammood and B. J. Mohammed, “Genetic Identifications for Sample of Multiple Sclerosis Iraqi Patients,” Iraqi J. Biotechnol., vol. 21, no. 2, pp. 225–235, 2022.
[16]    S. A. Abdulhameed and B. J. Mohammed, “The Relationship of Gene Expression between TNF and TNF-Like Cytokine 1A Genes in Sample of Multiple Sclerosis Iraqi Patients,” Iraqi J. Biotechnol., vol. 21, no. 2, pp. 88–95, 2022.
[17]    M. Khademi et al., “Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers,” PLoS One, vol. 8, no. 5, p. e63172, 2013.
[18]    M. A. Ali, O. G. Shaker, H. M. Eid, E. E. Mahmoud, E. M. Ezzat, and S. N. Gaber, “Relationship between miR‑155 and miR‑146a polymorphisms and susceptibility to multiple sclerosis in an Egyptian cohort,” Biomed. Reports, vol. 12, no. 5, pp. 276–284, 2020.
[19]    S. R. Mohammed et al., “Impact of miR-155 (rs767649 A> T) and miR-146a (rs57095329 A> G) polymorphisms in System Lupus Erythematosus susceptibility in an Egyptian cohort.,” Eur. Rev. Med. Pharmacol. Sci., vol. 25, no. 3, 2021.
[20]    R. Wang et al., “Association between genetic variants of microRNA‐21 and microRNA‐155 and systemic lupus erythematosus: A case‐control study from a Chinese population,” J. Clin. Lab. Anal., vol. 36, no. 7, p. e24518, 2022.
[21]    K. Xie et al., “A functional variant in miR-155 regulation region contributes to lung cancer risk and survival,” Oncotarget, vol. 6, no. 40, p. 42781, 2015.
[22]    J. Ji et al., “MiR-155 and its functional variant rs767649 contribute to the susceptibility and survival of hepatocellular carcinoma,” Oncotarget, vol. 7, no. 37, p. 60303, 2016.
[23]    Z. A. Aljawadi, A. R. Al-Derzi, B. A. Abdul-Majeed, and A. M. Almahdawi, “MicroRNAs (20a, 146a, 155, and 145) expressions in a sample of Iraqi patients with multiple sclerosis,” J. Fac. Med. Baghdad, vol. 58, no. 4, pp. 371–377, 2016.
[24]    W. W Kamphuis, C. Derada Troletti, A. Reijerkerk, I. A Romero, and H. E de Vries, “The blood-brain barrier in multiple sclerosis: microRNAs as key regulators,” CNS Neurol. Disord. Targets (Formerly Curr. Drug Targets-CNS Neurol. Disord., vol. 14, no. 2, pp. 157–167, 2015.
[25]    B. Shademan, A. Nourazarian, M. Nikanfar, C. B. Avci, M. Hasanpour, and A. Isazadeh, “Investigation of the miRNA146a and miRNA155 gene expression levels in patients with multiple sclerosis,” J. Clin. Neurosci., vol. 78, pp. 189–193, 2020.
[26]    V. Lyons, “The Role of miR-155 in Myeloid cells during Experimental Autoimmune Encephalomyelitis.” Trinity College Dublin Ireland, 2020.
[27]    A. Junker et al., “MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47,” Brain, vol. 132, no. 12, pp. 3342–3352, 2009.
[28]    D. Luo, J. Wang, X. Zhang, X. Rang, C. Xu, and J. Fu, “Identification and functional analysis of specific MS risk miRNAs and their target genes,” Mult. Scler. Relat. Disord., vol. 41, p. 102044, 2020.
[29]    L. D. Ward and M. Kellis, “HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants,” Nucleic Acids Res., vol. 40, no. D1, pp. D930–D934, 2012.