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Published in: BMC Medical Genetics 1/2012

Open Access 01-12-2012 | Research article

Association of IL-18 polymorphisms with rheumatoid arthritis and systemic lupus erythematosus in Asian populations: a meta-analysis

Authors: Shuilian Chen, Feng Jiang, Jiangping Ren, Jiajing Liu, Wei Meng

Published in: BMC Medical Genetics | Issue 1/2012

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Abstract

Background

Interleukin (IL)-18, an important proinflammatory cytokine, plays a potential pathological role in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Studies on the relationship of IL-18 gene promoter rs1946518 (−607A/C) polymorphism, rs187238 (−137G/C) polymorphism with RA and SLE are inconclusive. The aim of this study was to get a more precise estimation of the relationship in Asian populations.

Methods

Meta-analysis was conducted on the associations between the IL-18 (−607A/C and -137G/C) polymorphisms and RA and SLE, using; (1) allele contrast, (2) dominant, and (3) recessive models. A total of 11 studies were included in this study.

Results

For the relationship of IL-18 rs1946518 polymorphism with RA (additive model: OR=0.752, 95%CI=0.562-1.006; dominant model: OR=0.730, 95%CI =0.479-1.113; recessive model: OR=0.537, 95%CI=0.271-1.064) and SLE (additive model: OR=0.684, 95%CI=0.455-1.028; dominant model: OR=0.645, 95%CI=0.368-1.130; recessive model: OR=0.672, 95%CI =0.447-1.010), no significant association with RA and SLE risk can be found under all genetic models in Asian populations. However, significant associations were observed in Chinese population for both RA ((OR=0.688, 95%CI =0.532-0.889) and SLE (OR=0.606, 95%CI =0.396-0.930) under additive model. For the relationship between IL-18 rs187238 polymorphism and RA or SLE, there was no significant association detected in all genetic models, even in Chinese population.

Conclusions

This meta-analysis indicates that the IL-18-607A/C polymorphism may confer susceptibility to RA and SLE in Chinese population, but not all Asians.
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Literature
1.
go back to reference Sestak AL, Shaver TS, Moser KL, Neas BR, Harley JB: Familial aggregation of lupus and autoimmunity in an unusual multiplex pedigree. J Rheumatol. 1999, 26 (7): 1495-1499.PubMed Sestak AL, Shaver TS, Moser KL, Neas BR, Harley JB: Familial aggregation of lupus and autoimmunity in an unusual multiplex pedigree. J Rheumatol. 1999, 26 (7): 1495-1499.PubMed
2.
go back to reference Wandstrat A, Wakeland E: The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nat Immunol. 2001, 2 (9): 802-809. 10.1038/ni0901-802.CrossRefPubMed Wandstrat A, Wakeland E: The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nat Immunol. 2001, 2 (9): 802-809. 10.1038/ni0901-802.CrossRefPubMed
3.
go back to reference Lindqvist A, Alarcon-Riquelme ME: The genetics of systemic lupus erythematosus. Scand J Immunol. 1999, 50: 562-571. 10.1046/j.1365-3083.1999.00664.x.CrossRefPubMed Lindqvist A, Alarcon-Riquelme ME: The genetics of systemic lupus erythematosus. Scand J Immunol. 1999, 50: 562-571. 10.1046/j.1365-3083.1999.00664.x.CrossRefPubMed
4.
go back to reference Dinarello CA: IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immun. 1999, 103 (1): 11-24. 10.1016/S0091-6749(99)70518-X.CrossRefPubMed Dinarello CA: IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immun. 1999, 103 (1): 11-24. 10.1016/S0091-6749(99)70518-X.CrossRefPubMed
5.
go back to reference Gracie JA, Forsey RJ, Gilmour A, Leung BP, Greer MR, Kennedy K, Carter R, Wei XQ, Xu D: A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest. 1999, 104: 1393-1402. 10.1172/JCI7317.CrossRefPubMedPubMedCentral Gracie JA, Forsey RJ, Gilmour A, Leung BP, Greer MR, Kennedy K, Carter R, Wei XQ, Xu D: A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest. 1999, 104: 1393-1402. 10.1172/JCI7317.CrossRefPubMedPubMedCentral
6.
go back to reference Wong CK, Ho CY, Li EK, Lam C: Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000, 9 (8): 589-593. 10.1191/096120300678828703.CrossRefPubMed Wong CK, Ho CY, Li EK, Lam C: Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000, 9 (8): 589-593. 10.1191/096120300678828703.CrossRefPubMed
7.
go back to reference Yoshimoto T, Tsutsui H, Tominaga K, Hoshino K, Okamura H, Akira S, Paul WE, Nakanishi K: IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc Natl Acad Sci. 1999, 96 (24): 13962-10.1073/pnas.96.24.13962.CrossRefPubMedPubMedCentral Yoshimoto T, Tsutsui H, Tominaga K, Hoshino K, Okamura H, Akira S, Paul WE, Nakanishi K: IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc Natl Acad Sci. 1999, 96 (24): 13962-10.1073/pnas.96.24.13962.CrossRefPubMedPubMedCentral
8.
go back to reference Matsui K, Tsutsui H, Nakanishi K: Pathophysiological roles for IL-18 in inflammatory arthritis. Expert Opin Ther Targets. 2003, 7 (6): 701-724. 10.1517/14728222.7.6.701.CrossRefPubMed Matsui K, Tsutsui H, Nakanishi K: Pathophysiological roles for IL-18 in inflammatory arthritis. Expert Opin Ther Targets. 2003, 7 (6): 701-724. 10.1517/14728222.7.6.701.CrossRefPubMed
9.
go back to reference Wong CK, Ho CY, Li EK, Tam LS, Lam C: Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. Clin Exp Immunol. 2002, 130 (2): 345-351. 10.1046/j.1365-2249.2002.01989.x.CrossRefPubMedPubMedCentral Wong CK, Ho CY, Li EK, Tam LS, Lam C: Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. Clin Exp Immunol. 2002, 130 (2): 345-351. 10.1046/j.1365-2249.2002.01989.x.CrossRefPubMedPubMedCentral
10.
go back to reference Nolan KF, Greaves DR, Waldmann H: The human interleukin 18 gene IL18 maps to 11q22. 2-q22. 3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci. Genomics. 1998, 51 (1): 161-10.1006/geno.1998.5336.CrossRefPubMed Nolan KF, Greaves DR, Waldmann H: The human interleukin 18 gene IL18 maps to 11q22. 2-q22. 3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci. Genomics. 1998, 51 (1): 161-10.1006/geno.1998.5336.CrossRefPubMed
11.
go back to reference Huang XZ, Zhuang JH, Ren YG, Zhou LJ, Zhou Q: [Association of interleukin-6 and interleukin-18 gene polymorphism with rheumatoid arthritis in Guangdong Han population]. Nan Fang Yi Ke Da Xue Xue Bao. 2007, 27 (11): 1661-1664.PubMed Huang XZ, Zhuang JH, Ren YG, Zhou LJ, Zhou Q: [Association of interleukin-6 and interleukin-18 gene polymorphism with rheumatoid arthritis in Guangdong Han population]. Nan Fang Yi Ke Da Xue Xue Bao. 2007, 27 (11): 1661-1664.PubMed
12.
go back to reference Xu Q, Tin SK, Sivalingam SP, Thumboo J, Koh DR, Fong KY: Interleukin-18 promoter gene polymorphisms in Chinese patients with systemic lupus erythematosus: association with CC genotype at position −607. Ann Acad Med Singapore. 2007, 36 (2): 91-95.PubMed Xu Q, Tin SK, Sivalingam SP, Thumboo J, Koh DR, Fong KY: Interleukin-18 promoter gene polymorphisms in Chinese patients with systemic lupus erythematosus: association with CC genotype at position −607. Ann Acad Med Singapore. 2007, 36 (2): 91-95.PubMed
13.
go back to reference Lin YJ, Wan L, Lee CC, Huang CM, Tsai Y, Tsai CH, Shin TL, Chao K, Liu CM, Xiao JW, et al: Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients. Genes Immun. 2007, 8 (4): 302-307. 10.1038/sj.gene.6364387.CrossRefPubMed Lin YJ, Wan L, Lee CC, Huang CM, Tsai Y, Tsai CH, Shin TL, Chao K, Liu CM, Xiao JW, et al: Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients. Genes Immun. 2007, 8 (4): 302-307. 10.1038/sj.gene.6364387.CrossRefPubMed
14.
go back to reference Ying B, Shi Y, Pan X, Song X, Huang Z, Niu Q, Cai B, Wang L: Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep. 2011, 38 (1): 379-385. 10.1007/s11033-010-0119-x.CrossRefPubMed Ying B, Shi Y, Pan X, Song X, Huang Z, Niu Q, Cai B, Wang L: Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep. 2011, 38 (1): 379-385. 10.1007/s11033-010-0119-x.CrossRefPubMed
15.
go back to reference Tan EM, Cohen AS, Fries JF, Masi AT, Mcshane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25 (11): 1271-1277. 10.1002/art.1780251101.CrossRefPubMed Tan EM, Cohen AS, Fries JF, Masi AT, Mcshane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25 (11): 1271-1277. 10.1002/art.1780251101.CrossRefPubMed
16.
go back to reference Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997, 40 (9): 1725-CrossRefPubMed Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997, 40 (9): 1725-CrossRefPubMed
17.
go back to reference Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 2005, 31 (3): 315-324.CrossRef Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 2005, 31 (3): 315-324.CrossRef
18.
go back to reference Rothwell PM, Robertson G: Meta-analysis of randomised controlled trials. Lancet. 1997, 350 (9085): 1181-1182. 10.1016/S0140-6736(05)63832-9.CrossRefPubMed Rothwell PM, Robertson G: Meta-analysis of randomised controlled trials. Lancet. 1997, 350 (9085): 1181-1182. 10.1016/S0140-6736(05)63832-9.CrossRefPubMed
19.
20.
go back to reference DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7 (3): 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7 (3): 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed
21.
go back to reference Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. The Challenge of Epidemiology: Issues and Selected Readings. 2004, 1 (1): 533-553. Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. The Challenge of Epidemiology: Issues and Selected Readings. 2004, 1 (1): 533-553.
22.
go back to reference Harbord RM, Egger M, Sterne JAC: A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints. Stat Med. 2006, 25 (20): 3443-3457. 10.1002/sim.2380.CrossRefPubMed Harbord RM, Egger M, Sterne JAC: A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints. Stat Med. 2006, 25 (20): 3443-3457. 10.1002/sim.2380.CrossRefPubMed
23.
go back to reference Sivalingam SP, Yoon KH, Koh DR, Fong KY: Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid arthritis patients: protective effect of AA genotype. Tissue Antigens. 2003, 62 (6): 498-504. 10.1046/j.1399-0039.2003.00137.x.CrossRefPubMed Sivalingam SP, Yoon KH, Koh DR, Fong KY: Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid arthritis patients: protective effect of AA genotype. Tissue Antigens. 2003, 62 (6): 498-504. 10.1046/j.1399-0039.2003.00137.x.CrossRefPubMed
24.
go back to reference Ye ZH, Yin ZH, He WZ, Luo XX: Association of interleukin-18 promoter gene polymorphisms with systemic lupus erythematosus. J Practical Med. 2009, 25 (15): 2441-2443. Ye ZH, Yin ZH, He WZ, Luo XX: Association of interleukin-18 promoter gene polymorphisms with systemic lupus erythematosus. J Practical Med. 2009, 25 (15): 2441-2443.
25.
go back to reference Sugiura T, Kawaguchi Y, Ikari K, Ichida H, Kawamoto M, Momohara S, Hara M, Yamanaka H: Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis: protective effect of the T allele and T/T genotype at rs360722. Mod Rheumatol. 2011, 21 (4): 359-364. 10.1007/s10165-010-0399-y.CrossRefPubMed Sugiura T, Kawaguchi Y, Ikari K, Ichida H, Kawamoto M, Momohara S, Hara M, Yamanaka H: Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis: protective effect of the T allele and T/T genotype at rs360722. Mod Rheumatol. 2011, 21 (4): 359-364. 10.1007/s10165-010-0399-y.CrossRefPubMed
26.
go back to reference Shi P, Xiao LS, Fei Y, Yu F: Polymorphisms of IL-18 gene in rheumatoid arthitis and its association with rheumatoid factor or anti-cyclic citrulliated peptide antibody in Han population of Guizhou of China. Clinical Focus. 2011, 26 (4): 289-295. Shi P, Xiao LS, Fei Y, Yu F: Polymorphisms of IL-18 gene in rheumatoid arthitis and its association with rheumatoid factor or anti-cyclic citrulliated peptide antibody in Han population of Guizhou of China. Clinical Focus. 2011, 26 (4): 289-295.
27.
go back to reference Lan Y, Wei YS, Tang XS, Qin J, Wu J, Qin JM: [Association of interleukin-18 gene polymorphism with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008, 25 (4): 434-437.PubMed Lan Y, Wei YS, Tang XS, Qin J, Wu J, Qin JM: [Association of interleukin-18 gene polymorphism with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008, 25 (4): 434-437.PubMed
28.
go back to reference Chen DY, Hsieh CW, Chen KS, Chen YM, Lin FJ, Lan JL: Association of interleukin-18 promoter polymorphisms with WHO pathological classes and serum IL-18 levels in Chinese patients with lupus nephritis. Lupus. 2009, 18 (1): 29-37. 10.1177/0961203308094559.CrossRefPubMed Chen DY, Hsieh CW, Chen KS, Chen YM, Lin FJ, Lan JL: Association of interleukin-18 promoter polymorphisms with WHO pathological classes and serum IL-18 levels in Chinese patients with lupus nephritis. Lupus. 2009, 18 (1): 29-37. 10.1177/0961203308094559.CrossRefPubMed
29.
go back to reference Hirankarn N, Tangwattanachuleeporn M, Wongpiyabovorn J, Wongchinsri J, Avihingsanon Y: Association of IL-18 gene polymorphism (−137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A). Clin Rheumatol. 2009, 28 (2): 219-223. 10.1007/s10067-008-1036-4.CrossRefPubMed Hirankarn N, Tangwattanachuleeporn M, Wongpiyabovorn J, Wongchinsri J, Avihingsanon Y: Association of IL-18 gene polymorphism (−137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A). Clin Rheumatol. 2009, 28 (2): 219-223. 10.1007/s10067-008-1036-4.CrossRefPubMed
30.
go back to reference Pan HF, Leng RX, Ye DQ: Lack of association of interleukin-18 gene promoter-607 A/C polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Lupus. 2011, 20 (9): 945-951. 10.1177/0961203311400114.CrossRefPubMed Pan HF, Leng RX, Ye DQ: Lack of association of interleukin-18 gene promoter-607 A/C polymorphism with susceptibility to autoimmune diseases: a meta-analysis. Lupus. 2011, 20 (9): 945-951. 10.1177/0961203311400114.CrossRefPubMed
31.
go back to reference Haus-Seuffert P, Meisterernst M: Mechanisms of transcriptional activation of cAMP-responsive element-binding protein CREB. Mol Cell Biochem. 2000, 212 (1): 5-9. 10.1023/A:1007111818628.CrossRefPubMed Haus-Seuffert P, Meisterernst M: Mechanisms of transcriptional activation of cAMP-responsive element-binding protein CREB. Mol Cell Biochem. 2000, 212 (1): 5-9. 10.1023/A:1007111818628.CrossRefPubMed
32.
go back to reference 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, 112 (1–2): 146-152.CrossRefPubMed 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, 112 (1–2): 146-152.CrossRefPubMed
33.
go back to reference Dziedziejko V, Kurzawski M, Paczkowska E, Machalinski B, Pawlik A: The impact of IL18 gene polymorphisms on mRNA levels and interleukin-18 release by peripheral blood mononuclear cells. Postepy Hig Med Dosw (Online). 2012, 66: 409-414.CrossRef Dziedziejko V, Kurzawski M, Paczkowska E, Machalinski B, Pawlik A: The impact of IL18 gene polymorphisms on mRNA levels and interleukin-18 release by peripheral blood mononuclear cells. Postepy Hig Med Dosw (Online). 2012, 66: 409-414.CrossRef
Metadata
Title
Association of IL-18 polymorphisms with rheumatoid arthritis and systemic lupus erythematosus in Asian populations: a meta-analysis
Authors
Shuilian Chen
Feng Jiang
Jiangping Ren
Jiajing Liu
Wei Meng
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2012
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-13-107

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