The association between interleukin-6 polymorphisms and rheumatoid arthritis: a meta-analysis
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The aim of this study was to determine whether the functional interleukin-6 (IL-6) promoter −174 G/C and −572 G/C polymorphisms confer susceptibility to rheumatoid arthritis (RA) in ethnically different populations.
Meta-analysis was conducted on the associations between these IL-6 polymorphisms and RA.
A total of nine studies involving 3,851 subjects (RA 2,053 and controls 1,798) were considered in this study and ethnicity-specific meta-analysis was performed on European subjects. In all study subjects, meta-analysis revealed a trend toward to an association between RA and the IL-6 −174 G allele (odds ratio [OR] = 0.699, 95 % confidence interval [CI] = 0.463–1.054, p = 0.088). Stratification by ethnicity indicated a significant association between RA and the IL-6 −174 G/C polymorphism in Europeans using the dominant (OR = 0.329, 95 % CI = 0.155–0.699, p = 0.004) and recessive (OR = 0.823, 95 % CI = 0.679–0.997, p = 0.047) models. Meta-analysis of the IL-6 −572 G/C polymorphism showed no association between RA and the IL-6 −572 G allele in all study subjects (OR = 1.641, 95 % CI = 0.613–4.397, p = 0.324).
This meta-analysis shows that the IL-6 −174 G/C polymorphism may confer susceptibility to RA in Europeans.
KeywordsInterleukin-6 Polymorphism Rheumatoid arthritis Meta-analysis
This study is supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065).
Conflict of interest
The authors have no financial and non-financial conflicts of interest to declare.
- 2.Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661-678.Google Scholar
- 5.Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67:1516–23.PubMedCrossRefGoogle Scholar
- 6.Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102:1369–76.PubMedCrossRefGoogle Scholar
- 7.Arman A, Coker A, Sarioz O, Inanc N, Direskeneli H. Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish population. Rheumatol Int. 2011 (Epub ahead of print) http://dx.doi.org/10.1007/s00296-011-2057-x.
- 8.Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Llorca J, Martin J, Gonzalez-Gay MA. Interleukin-6 gene −174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2009;27:964–70.PubMedGoogle Scholar
- 10.Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Milionis HJ, Douglas KM, Nightingale P, Kitas GD. Association of interleukin-6 (IL-6) −174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis. 2009;204:178–83.PubMedCrossRefGoogle Scholar
- 15.Fugger L, Morling N, Bendtzen K, Ryder L, Andersen V, Heilman C, Karup Pedersen F, Friis J, Halbert P, Svejgaard A. IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. J Immunogenet. 1989;16:461–5.PubMedCrossRefGoogle Scholar
- 23.Lopez-Mejias R, Garcia-Bermudez M, Gonzalez-Juanatey C, Castaneda S, Perez-Esteban S, Miranda-Filloy JA, Gomez-Vaquero C, Fernandez-Gutierrez B, Balsa A, Pascual-Salcedo D, Blanco R, Gonzalez-Alvaro I, Llorca J, Martin J, Gonzalez-Gay MA. Lack of association between IL6 single nucleotide polymorphisms and cardiovascular disease in Spanish patients with rheumatoid arthritis. Atherosclerosis. 2011;219:655–8.PubMedCrossRefGoogle Scholar
- 28.Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2011) Association between the CTLA-4 +49 A/G polymorphism and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep (Epub ahead of print) doi: 10.1007/s11033-011-1364-3
- 30.Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjogren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford). 2001;40:656–61.CrossRefGoogle Scholar
- 31.Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L, Rumley A, Lowe GD, Humphries SE. Interleukin-6 gene −174g > c and −572g > c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol. 2001;21:1458–63.PubMedCrossRefGoogle Scholar
- 33.Sie MP, Sayed-Tabatabaei FA, Oei HH, Uitterlinden AG, Pols HA, Hofman A, van Duijn CM, Witteman JC. Interleukin 6–174 g/c promoter polymorphism and risk of coronary heart disease: results from the Rotterdam study and a meta-analysis. Arterioscler Thromb Vasc Biol. 2006;26:212–7.PubMedCrossRefGoogle Scholar