Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population

Author(s): Rashin Ganjali, Jalil T. Afshari, Zahra Rezaieyazdi*, Mandana Khodashahi, Azam Brook, Maryam Mazhani, Mohamad R. Hatef and Mahnaz Abbasi

Volume 16, Issue 2, 2020

Page: [105 - 109] Pages: 5

DOI: 10.2174/1573397116666191218100556

Price: $65

Abstract

Objectives: Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran.

Methods: Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene.

Results: Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29).

Conclusion: Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

Keywords: Systemic lupus erythematosus, interleukin-1, receptor, antagonist, genes, polymorphism, gene polymorphism.

Next »
Graphical Abstract
[1]
Rees F, Doherty M, Grainge M, Davenport G, Lanyon P, Zhang W. The incidence and prevalence of systemic lupus erythematosus in the UK, 1999-2012. Ann Rheum Dis 2016; 75(1): 136-41.
[http://dx.doi.org/10.1136/annrheumdis-2014-206334] [PMID: 25265938]
[2]
Dougados M. Comorbidities in rheumatoid arthritis. Curr Opin Rheumatol 2016; 28(3): 282-8.
[http://dx.doi.org/10.1097/BOR.0000000000000267] [PMID: 27027814]
[3]
Jacob N, Stohl W. Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: past, present, and future. Autoimmunity 2010; 43(1): 84-97.
[http://dx.doi.org/10.3109/08916930903374600] [PMID: 20014977]
[4]
Wakeland EK, Liu K, Graham RR, Behrens TW. Delineating the genetic basis of systemic lupus erythematosus. Immunity 2001; 15(3): 397-408.
[http://dx.doi.org/10.1016/S1074-7613(01)00201-1] [PMID: 11567630]
[5]
Tsao BP, Grossman JM. Genetics and systemic lupus erythematosus.Curr Rheumatol Rep 2001; 3(3): 183-90.
[http://dx.doi.org/10.1007/s11926-001-0017-2] [PMID: 11352786]
[6]
Fronek Z, Timmerman LA, Alper CA, et al. Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus.Arthritis Rheum 1990; 33(10): 1542-53.
[http://dx.doi.org/10.1002/art.1780331012] [PMID: 1977392]
[7]
Galeazzi M, Sebastiani GD, Morozzi G, et al. European Concertee Action on the immunogenetics of SLE. HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets. Medicine (Baltimore) 2002;; 81(3): 169-78.
[http://dx.doi.org/10.1097/00005792-200205000-00001] [PMID: 11997714]
[8]
Jönsen A, Bengtsson AA, Sturfelt G, Truedsson L. Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility. Arthritis Res Ther 2004; 6(6): R557-62.
[http://dx.doi.org/10.1186/ar1224] [PMID: 15535834]
[9]
Hutyrová B, Pantelidis P, Drábek J, et al. Interleukin-1 gene cluster polymorphisms in sarcoidosis and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002; 165(2): 148-51.
[http://dx.doi.org/10.1164/ajrccm.165.2.2106004] [PMID: 11790645]
[10]
Grover S, Tandon S, Misra R, Aggarwal A. Interleukin-1 receptor antagonist gene polymorphism in patients with rheumatoid arthritis in India. Indian J Med Res 2006; 123(6): 815-20.
[PMID: 16885604]
[11]
Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 1998; 16: 27-55.
[http://dx.doi.org/10.1146/annurev.immunol.16.1.27] [PMID: 9597123]
[12]
Tarlow JK, Blakemore AI, Lennard A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993; 91(4) 403-4.
[http://dx.doi.org/10.1007/BF00217368] [PMID: 8500797]
[13]
Tahmasebi Z, Akbarian M, Mirkazemi S, et al. Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus. Rheumatol Int 2013; 33(10): 2591-6.
[http://dx.doi.org/10.1007/s00296-013-2784-2] [PMID: 23722873]
[14]
Rönnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B. Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcgammaRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE. Ann Rheum Dis 2003; 62(1): 37-42.
[http://dx.doi.org/10.1136/ard.62.1.37] [PMID: 12480667]
[15]
Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349(16): 1526-33.
[http://dx.doi.org/10.1056/NEJMoa021933] [PMID: 14561795]
[16]
Dinarello CA. Introduction to the interleukin-1 family of cytokines and receptors: Drivers of innate inflammation and acquired immunity. Immunol Rev 2018; 281(1): 5-7.
[http://dx.doi.org/10.1111/imr.12624] [PMID: 29248001]
[17]
Panneer D, Antony PT, Palamalai SR, Negi VS. Interleukin 1 receptor antagonist (IL1Ra) VNTR polymorphism influences circulatory IL1Ra levels and development of SLE in South Indian Tamils.Indian Journal of Rheumatology 2016; 11(1): 2-6.
[http://dx.doi.org/10.1016/j.injr.2015.10.003]
[18]
Brunner HI, Holland M, Beresford MW, Ardoin SP, Appenzeller S, Silva CA, et al. American College of Rheumatology Provisional Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus 2018; 70(6): 813-22.
[19]
Brunner HI, Holland MJ, Beresford MW, Ardoin SP, Appenzeller S, Silva CA, et al. The American College of Rheumatology Provisional criteria for clinically relevant improvement in children & adolescents with childhood-onset systemic lupus erythematosus Arthritis Care Res (Hoboken) 2019.
[http://dx.doi.org/10.1002/acr.23834]
[20]
Lahiri DK, Nurnberger JI Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 1991; 19(19): 5444.
[http://dx.doi.org/10.1093/nar/19.19.5444] [PMID: 1681511]
[21]
Witkin SS, Gerber S, Ledger WJ. Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin Infect Dis 2002; 34(2): 204-9.
[http://dx.doi.org/10.1086/338261] [PMID: 11740709]
[22]
Italiani P, Manca ML, Angelotti F, et al. IL-1 family cytokines and soluble receptors in systemic lupus erythematosus. Arthritis Res Ther 2018; 20(1): 27-7.
[http://dx.doi.org/10.1186/s13075-018-1525-z] [PMID: 29422069]
[23]
Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2011; 31(10): 781-9.
[http://dx.doi.org/10.1089/jir.2011.0047]
[24]
Lee YH, Kim HJ, Rho YH, Choi SJ, Ji JD, Song GG. Interleukin-1 receptor antagonist gene polymorphism and rheumatoid arthritis.Rheumatol Int 2004; 24(3): 133-6.
[http://dx.doi.org/10.1007/s00296-003-0337-9] [PMID: 14872281]
[25]
Mohammadoo-Khorasani M, Salimi S, Tabatabai E, Sandoughi M, Zakeri Z. Association of interleukin-1 receptor antagonist gene 86bp VNTR polymorphism with systemic lupus erythematosus in south east of Iran. Zahedan J Res Med Sci 2013; 16(12)
[26]
Cai L, Zhang JW, Xue XX, et al. Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility. PLoS One 2014; 9(10) e109712.
[http://dx.doi.org/10.1371/journal.pone.0109712] [PMID: 25286391]
[27]
Kamenarska Z, Dzhebir G, Hristova M, Savov A, Vinkov A, Kaneva R, et al. IL-1RN VNTR Polymorphism in adult dermatomyositis and systemic lupus erythematosus Dermatology research and practice 2014; 2014
[28]
Gordon C. Long-term complications of systemic lupus erythematosus.Rheumatology (Oxford) 2002; 41(10): 1095-0.
[http://dx.doi.org/10.1093/rheumatology/41.10.1095] [PMID: 12364626]
[29]
Mukherjee S. Long term complications in systemic lupus erythematosus.Journal-Association Physicians India 2006; 54(N): 22.
[30]
Kamenarska Z, Dzhebir G, Hristova M, et al. IL-1RN VNTR Polymorphism in Adult Dermatomyositis and Systemic Lupus Erythematosus. Dermatol Res Pract 2014; 2014: 953597-7.
[http://dx.doi.org/10.1155/2014/953597] [PMID: 25328514]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy