 |
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2020, vol. 26, issue4
Subject Area: Medicine
-
DOI: 10.5272/jimab.2020264.3475
Published online: 01 December 2020
Original article
J of IMAB. 2020 Oct-Dec;26(4):3475-3480
IL-18 PROMOTER POLYMORPHISM AND IL-18 SERUM LEVELS IN ASSOCIATION WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS
Boncho Grigorov1
, Anastasiya Trenova2, Antonia Grigorova1, Spaska Stanilova1,
1) Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty Trakia University, Stara Zagora, Bulgaria
2) Department of Neurology, Faculty of Medicine, Medical University of Plovdiv, Bulgaria.
ABSTRACT:
Purpose: Multiple sclerosis is the immune-mediated disorder whose etiology is not completely understood. The present study aimed to survey association between the promoter polymorphism IL18 -607C/A (rs1946518), the serum concentration of IL-18 and susceptibility to relapsing-remitting multiple sclerosis (RRMS) in Bulgarian patients
Material and Methods: This case-control study includes 159 RRMS patients with disease-modifying therapy (DMT) and 162 age-sex-matched healthy volunteers. All included subjects were genotyped by ARMS-PCR while serum levels were measured by enzyme-linked immunosorbent assay (ELISA).
Results: Our results revealed significant differences in the serum levels of IL-18 according to the gender, the onset of disease and the type of disease-modifying therapy. The serum levels of IL-18 are significantly higher in RRMS men compared to RRMS women and the RRMS men with late-onset of the disease (above 30 years) also demonstrated significantly increased serum levels than the women with late-onset of disease and even with healthy men. The RRMS patients treated with interferon-beta showed significantly increased IL-18 serum level than those treated with glatiramer acetate.
Conclusions: Our study shows that the promoter polymorphism IL18 -607C/A is not associated with susceptibility to RRMS in Bulgarian patients as well as the serum level of the cytokine. The observed differences in the serum level of IL-18 in RRMS patients according to gender and the response to therapy could be used as a biomarker to the course of the disease.
Keywords: relapsing-remitting multiple sclerosis, cytokine, rs1946518, SNP,
- Download FULL TEXT /PDF 644 KB/
Please cite this article as: Grigorov B, Trenova A, Grigorova A, Stanilova S. IL-18 promoter polymorphism and IL-18 serum levels in association with relapsing-remitting multiple sclerosis. J of IMAB. 2020 Oct-Dec;26(4):3475-3480. DOI: 10.5272/jimab.2020264.3475
Correspondence to: Boncho Grigorov, PhD, Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty Trakia University; 11 Armyayska Str., 6000 Stara Zagora, Bulgaria; E-mail: boncho.g@gmail.com
REFERENCES:
1. Berer K, Krishnamoorthy G. Microbial view of central nervous system autoimmunity. FEBS Lett. 2014 Nov 17;588(22):4207-13. [PubMed] [Crossref]
2. Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. [PubMed] [Crossref]
3. Babaloo Z, Aliparasti M, Babaiea F, Almasi S, Baradaran B, Farhoudi M. The role of Th17 cells in patients with relapsing-remitting multiple sclerosis: interleukin-17A and interleukin-17F serum levels. Immunol Lett. 2015 Apr;164(2):76-80. [PubMed] [Crossref]
4. Arellano G, Ottum PA, Reyes LI, Burgos PI, Naves R. Stage-Specific Role of Interferon-Gamma in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. Front immunol. 2015 Sept 29;6:492. [PubMed] [Crossref]
5. Baker KJ, Houston A, Brint E. IL-1 Family Members in Cancer; Two Sides to Every Story. Front Immunol. 2019 Jun 7;10:1197. [PubMed] [Crossref]
6. Swain SL. Interleukin 18: tipping the balance towards a T helper cell 1 response. J Exp Med. 2001 Aug 6;194(3): F11-4. [PubMed] [Crossref]
7. Yuanyuan G, Xue Y, Yachao L, Xiao F, Xu C. Association between IL-18 -607 C/A Polymorphism and the Risk of Prostate Cancer: A Meta-Analysis of Case-Control Studies. Asian Pac J Cancer Prev. 2019 Jun 1;20(6):1595-1602. [PubMed] [Crossref]
8. Orhan G, Eruyar E, Mungan SO, Ak F, Karahalil B. The association of IL-18 gene promoter polymorphisms and the levels of serum IL-18 on the risk of multiple sclerosis. Clin Neurol neurosurg. 2016 Jul;146:96-101. [PubMed] [Crossref]
9. Taheri M, Hashemi M, Eskandari-Nasab E, Fazaeli A, Arababi F, Bahrani-Zeidabadi M, et al. Association of-607 C/A polymorphism of IL-18 gene (rs1946518) with breast cancer risk in Zahedan, Southeast Iran. Prague Med Rep. 2012; 113(3):217-22. [PubMed] [Crossref]
10. Giedraitis V, He B, Huang WX, Hillert J. Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol. 2001 Jan 1;112(1-2):146-52. [PubMed] [Crossref]
11. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292–302. [PubMed] [Crossref]
12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–52. [PubMed] [Crossref]
13. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 2001 Mar;12(1):53–72. [PubMed] [Crossref]
14. Chen YC, Chen SD, Miao L, Liu ZG, Li W, Zhao ZX, et al. Serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with multiple sclerosis. J Neuroimmunol. 2012 Feb 29;243(1-2):56-60. [PubMed] [Crossref]
15. Balasa R, Maier S, Voidazan S, Hutanu A, Bajko Z, Motataianu A, et al. Assessment of Interleukin-17A, Interleukin-10 and Transforming Growth Factor-Beta1 Serum Titers in Relapsing Remitting Multiple Sclerosis Patients Treated with Avonex, Possible Biomarkers for Treatment Response. CNS Neurol Disord Drug Targets. 2017; 16(1):93-101. [PubMed]
16. Keane RW, Dietrich WD, de Rivero Vaccari JP. Inflammasome Proteins As Biomarkers of Multiple Sclerosis. Front Neurol. 2018 Mar 19;9:135. [PubMed] [Crossref]
17. Losy J, Michalowska-Wender G, Wender M. Interleukin 12 and interleukin 10 are affected differentially by treatment of multiple sclerosis with glatiramer acetate (Copaxone). Folia neuropathol. 2002;40(4):173-5. [PubMed].
Received: 24 October 2019
Published online: 01 December 2020