Articles
 

Association between Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Pulmonary Tuberculosis

Abstract

Macrophages and T-lymphocytes are involved in immune response to Mycobacterium tuberculosis. Macrophage produces interleukin (IL)-1 as an inflammatory mediator. IL-1 receptor antagonist (IL1-Ra) is a natural antagonist of IL-1 receptors. In this study we aimed to examine the possible association between the variable number of tandem repeats (VNTR) of the IL-1 receptor antagonist (IL1RN) gene and pulmonary tuberculosis (TB) in a sample of Iranian population. Our study is a case-control study and we examined the VNTR of the IL1RN gene in 265 PTB and 250 healthy subjects by PCR. Neither the overall chi-square comparison of PTB and control subjects nor the logistic regression analysis indicated any association between VNTR IL1RN polymorphism and PTB. Our data suggest that VNTR IL1RN polymorphism may not be associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are needed to find out the impact of IL1RN VNTR polymorphism on risk of developing TB.

1. Barry CE, 3rd, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009; 7(12):845-55.
2. Stein CM. Genetic epidemiology of tuberculosis susceptibility: impact of study design. PLoS Pathog 2011;7(1):e1001189.
3. de Wit E, van der Merwe L, van Helden PD, Hoal EG.Gene-gene interaction between tuberculosis candidate genes in a South African population. Mamm Genome 2011; 22(1-2):100-10.
4. Hashemi M, Sharifi-Mood B, Nezamdoost M, Moazeni- Roodi A, Naderi M, Kouhpayeh H, et al. Functional polymorphism of interferon-gamma (IFN-gamma) gene +874T/A polymorphism is associated with pulmonary tuberculosis in Zahedan, Southeast Iran. Prague Med Rep 2011; 112(1):38-43.
5. Hashemi M, Eskandari-Nasab E, Moazeni-Roodi A, Naderi M, Sharifi-Mood B, Taheri M. Association of CTSZ rs34069356 and MC3R rs6127698 gene polymorphisms with pulmonary tuberculosis. Int J Tuberc Lung Dis 2013; 17(9):1224-8.
6. Naderi M, Hashemi M, Taheri M, Pesarakli H, Eskandari- Nasab E, Bahari G. CD209 promoter -336 A/G (rs4804803) polymorphism is associated with susceptibility to pulmonary tuberculosis in Zahedan, southeast Iran. J Microbiol Immunol Infect 2014;47(3):171-5.
7. Awomoyi AA, Charurat M, Marchant A, Miller EN, Blackwell JM, McAdam KP, et al. Polymorphism in IL1B: IL1B-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1beta in IFN- gamma primed ex-vivo whole blood assay. J Endotoxin Res 2005; 11(5):281-6.
8. Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE. Four new members expand the interleukin-1 superfamily. J Biol Chem 2000; 275(2):1169-75.
9. Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, et al. The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region. Genomics 1993; 15(1):173-6.
10. Fischer E, Van Zee KJ, Marano MA, Rock CS, Kenney JS, Poutsiaka DD, et al. Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 1992; 79(9):2196-200.
11. McIntyre KW, Stepan GJ, Kolinsky KD, Benjamin WR, Plocinski JM, Kaffka KL, et al. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med 1991; 173(4):931-9.
12. Xue J, Mou L, Lu X, Wu H. No association of interleukin-1 receptor antagonist VNTR polymorphism and rheumatoid arthritis susceptibility: a meta analysis. Clin Exp Rheumatol 2010; 28(5):654-60.
13. Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, et al. Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis. J Exp Med 1999; 189(12):1863-74.
14. Sugisaki K, Dannenberg AM, Jr., Abe Y, Tsuruta J, Su WJ, Said W, et al. Nonspecific and immune-specific up- regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. J Leukoc Biol 1998; 63(4):440-50.
15. Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P.The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989;56(5):731-40.
16. Arend WP, Malyak M, Guthridge CJ, Gabay C.Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol. 1998;16(27-55.
17. Granowitz EV, Clark BD, Mancilla J, Dinarello CA.Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem. 1991;266(22):14147-50.
18. Hurme M, Santtila S. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;28(8):2598-602.
19. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Tuber Lung Dis.1998;79(2):83-9.
20. Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer 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.
21. Danis VA, Millington M, Hyland VJ, Grennan D.Cytokine production by normal human monocytes: inter- subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol. 1995;99(2):303-10.
22. Clay FE, Tarlow JK, Cork MJ, Cox A, Nicklin MJ, Duff GW. Novel interleukin-1 receptor antagonist exon polymorphisms and their use in allele-specific mRNA assessment. Hum Genet. 1996;97(6):723-6.
23. Dewberry R, Holden H, Crossman D, Francis S.Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20(11):2394-400.
24. Whyte M, Hubbard R, Meliconi R, Whidborne M, Eaton V, Bingle C, et al. Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms. Am J Respir Crit Care Med. 2000;162(2 Pt 1):755-8.
25. Fenton MJ, Vermeulen MW. Immunopathology of tuberculosis: roles of macrophages and monocytes. Infect Immun. 1996;64(3):683-90.
26. Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood. 1991;77(8):1627-52.
27. Dinarello CA. Modalities for reducing interleukin 1 activity in disease. Immunol Today. 1993;14(6):260-4.

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IssueVol 14, No 1 (2015) QRcode
SectionArticles
Keywords
IL1RN Polymorphism Tuberculosis VNTR

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How to Cite
1.
Hashemi M, Naderi M, Ebrahimi M, Amininia S, Bahari G, Taheri M, Eskandari-Nasab E, Ghavami S. Association between Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Pulmonary Tuberculosis. Iran J Allergy Asthma Immunol. 1;14(1):55-59.