Articles

Association Between IL6-174 G/C Polymorphism and Graves' Disease: A Systematic Review and Meta-Analysis

Abstract

Several studies have evaluated the association between interleukin-6 (IL-6) -174 G/C polymorphism and Graves' disease (GD); however, the results have been inconsistent. In the current study, a meta-analysis was performed to assess the association of IL6 -174 G/C polymorphism with Graves' disease. Medline, EMBASE, and Web of Science databases were searched to identify all eligible studies published before August 2016. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to assess the strength of association in dominant, recessive, allelic, homozygotes contrast, and heterozygotes contrast models. A total of four case-control studies with 554 GD cases and 1201 healthy controls were included in this meta-analysis. In the combined analysis, the results showed significant association between the IL6 -174 G/C polymorphism and the risk for GD in dominant model (OR=1.39, 95% CI: 1.07-1.80), recessive model (OR=2.75, 95% CI: 1.01-7.55) and homozygote contrast model (OR=3.25, 95% CI: 1.1-9.58). No publication bias was found in the current study (all P>0.05). The meta-analysis results suggested that the IL6 -174 G/C polymorphism was indicated to be associated with the risk of GD. Further studies are warranted to confirm these results.

Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol 2014;9:147.

Anvari M, Khalilzadeh O, Esteghamati A, Esfahani S, Rashidi A, Etemadi A, et al. Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes. Eye 2010;24:1058-63.

Marinò M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol investigat 2015;38:283-94.

Latrofa F, Ricci D, Montanelli L, Piaggi P, Mazzi B, Bianchi F, et al. SAT-0538: Thyroglobulin Autoantibodies Switch to IgG1 and IgG3 Subclasses after 131I Treatment for Graves' Hyperthyroidism: Autoantibodies Subclasses Are Related to the Activity of Autoimmune Thyroid Disease. (Accessed April 2017, 29, at http://www.endocrine.org/meetings/endo-annual-meetings/abstract-details?ID=12882.)

Gastaldi R, Poggi E, Mussa A, Weber G, Vigone MC, Salerno M, et al. Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers. J Pediatr 2014;164:1189-94 .

Chen RH, Chen WC, Wang TY, Tsai CH, Tsai FJ. Lack of association between pro‐inflammatory cytokine (IL‐6, IL‐8 and TNF‐α) gene polymorphisms and Graves’ disease. Int J Immunogenet 2005;32:343-7.

Mosmann T, Coffman R. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-73.

GarcÍa-López MAn, Sancho D, Sánchez-Madrid F, Marazuela M. Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3+ lymphocytes. J Clin Endocrinol Metab 2001;86:5008-16.

Khalilzadeh O, Anvari M, Momen-Heravi F, Esteghamati A, Rashidi A, Mahmoudi M, et al. Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease. Clin Exp Med 2010;10:123-8.

Anvari M, Khalilzadeh O, Esteghamati A, Momen-Heravi F, Mahmoudi M, Esfahani SA, et al. Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ. Endocrine 2010;37:344-8.

Salvi M, Pedrazzoni M, Girasole G, Giuliani N, Minelli R,Roti E. Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking. Eur J Endocrinolo 2000;143:197-202.

Khalilzadeh O, Anvari M, Esteghamati A, Momen-Heravi F, Mahmoudi M, Rashidi A, et al. editors. The interleukin-1 family gene polymorphisms and Graves’ disease. Ann Endocrinol 2010;71:281-5.

Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro-and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011;1813:878-88.

McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology. Nat Immunol 2007;8:1390-7.

Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, et al. 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 Investigat 1998;102:1369.

Pereira D, Garcia D, Narciso F, Santos M, Dias J, Queiroz B, et al. Effects of 174 G/C polymorphism in the promoter region of the interleukin-6 gene on plasma IL-6 levels and muscle strength in elderly women. Braz J Med Biol Res 2011;44:123-9.

Pascual M, Nieto A, Mataran L, Balsa A, Pascual-Salcedo D, Martin J. IL-6 promoter polymorphisms in rheumatoid arthritis. Genes Immun 2000;1:338-40.

Sen A, Paine SK, Chowdhury IH, Mukherjee A, Choudhury S, Saha A, et al. Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level on the acute inflammation and neovascularization stages of patients with Eales’ disease. Mol Vis 2011;17:2552-63.

Totaro F, Cimmino F, Pignataro P, Acierno G, De Mariano M, Longo L, et al. Impact of interleukin-6–174 G> C gene promoter polymorphism on neuroblastoma. PloS One 2013;8:e76810.

Białecka M, Ostasz R, Kurzawski M, Klimowicz A, Fabiańczyk H, Bojko P, et al. IL6− 174G> C polymorphism is associated with an increased risk of psoriasis but not response to treatment. Exp Dermatol 2015;24:146-7.

Santos MJ, Fernandes D, Capela S, Da Silva JC, Fonseca JE. Interleukin-6 promoter polymorphism− 174 G/C is associated with nephritis in Portuguese Caucasian systemic lupus erythematosus patients. Clin Rheumatol 2011;30:409-13.

Angelakopoulou A, Shah T, Sofat R, Shah S, Berry DJ, Cooper J, et al. Comparative analysis of genome-wide association studies signals for lipidscoronary heart disease: Cardiovascular Biomarker Genetics Collaboration. Eur Heart J 2012;33:393-407.

Spasojević-Dimitrijeva B, Živković M, Stanković A, Stojković L, Kostić M. The IL-6− 174G/C polymorphism and renal scarring in children with first acute pyelonephritis. Pediatr Nephrol 2010;25:2099-106.

Bednarczuk T, Kuryłowicz A, Hiromatsu Y, Kiljański J, Telichowska A, Nauman J. Association of G-174C polymorphism of the interleukin-6 gene promoter with Graves' ophthalmopathy. Autoimmunity 2004;37:223-6.

Durães C, Moreira CS, Alvelos I, Mendes A, Santos LR, Machado JC, et al. Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease. PloS One 2014;9:e105492.

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008-12.

Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603-5.

Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet] 2005;76:887-93.

Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I² index? Psychol Methods 2006;11:193.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.

Boelaert K, Franklyn J. Thyroid hormone in health and disease. J Endocrinol 2005;187:1-15.

Weetman AP. Autoimmune thyroid disease: propagation and progression. Eur J Endocrinol 2003;148:1-9.

Salvi M, Girasole G, Pedrazzoni M, Passeri M, Giuliani N, Minelli R, et al. Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves' disease. The J Clin Endocrinol Metab 1996;81:2976-9.

.Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002;13:357-68.

Urashima M, Chauhan D, Hatziyanni M, Ogata A, Hollenbaugh D, Aruffo A, et al. CD40 ligand triggers interleukin-6 mediated B cell differentiation. Leuk Res 1996;20:507-15.

Özgen A, Karadeniz M, Erdogan M, Berdeli A, Saygili F, Yilmaz C. The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients .J Endocrinol Invest 2009;32:491-4.

Dienz O, Eaton SM, Bond JP, Neveu W, Moquin D, Noubade R, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. J Exp Med 2009;206:69-78.

Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid 2008;18:953-8.

Files
IssueVol 55, No 11 (2017) QRcode
SectionArticles
Keywords
Interleukin-6 Polymorphism Graves Meta-analysis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Imani D, Rezaei R, Razi B, Alizadeh S, Mahmoudi M. Association Between IL6-174 G/C Polymorphism and Graves’ Disease: A Systematic Review and Meta-Analysis. Acta Med Iran. 2018;55(11):665-671.