Skip to main content

Advertisement

SpringerLink
Log in

Association between TNF-α promoter –308 A/G polymorphism and rheumatoid arthritis: a meta-analysis

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The aim of this study was to determine whether the tumor necrosis factor-α (TNF-α) promoter –308 A/G polymorphism is associated with susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. MEDLINE and EMBASE databases and manual search were used to identify articles in which TNF-α polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the TNF-α –308 A/G polymorphism and RA by using (1) allelic contrast and (2) dominant models. A total of 19 studies involving 2,584 RA patients and 3,254 controls were considered. The meta-analysis showed no association between the TNF-α –308 A allele and RA when all the subjects were considered [odds ratio (OR) = 1.129, 95 % CI 0.843–1.513, P = 0.416]. After stratification by ethnicity, the meta-analysis indicated that the A allele was significantly associated with RA in Latin Americans (OR = 1.620, 95 % CI 1.234–2.111, P = 3.6 × 10−5), but not in the European, Arab, or Asian populations. The meta-analysis of the AA/AG genotype showed the same pattern of results as with the A allele. No association was noted between the AA/AG genotype and RA when all the subjects were considered (OR = 1.114, 95 % CI 0.812–1.529, P = 0.503), but stratification by ethnicity revealed that the AA/AG genotype was significantly associated with RA in Latin Americans (OR = 1.650, 95 % CI 1.234–2.104, P = 0.001). This meta-analysis showed that the TNF-α –308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans but not in the European, Arab, or Asian populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Harris ED Jr (1990) Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med 322(18):1277–1289

    Article  PubMed  Google Scholar 

  2. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatol Oxf 45(2):166–170

    Article  CAS  Google Scholar 

  3. Rooney M, David J, Symons J, Di Giovine F, Varsani H, Woo P (1995) Inflammatory cytokine responses in juvenile chronic arthritis. Br J Rheumatol 34(5):454–460

    Article  CAS  PubMed  Google Scholar 

  4. Allen RD (1999) Polymorphism of the human TNF-alpha promoter–random variation or functional diversity? Mol Immunol 36(15–16):1017–1027

    Article  CAS  PubMed  Google Scholar 

  5. D’Alfonso S, Richiardi PM (1994) A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 39(2):150–154

    PubMed  Google Scholar 

  6. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94(7):3195–3199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Boechat AL, Boechat Nde O, Ogusku MM, Alencar MR, Abensur Tda C, Cardoso Neto J et al (2013) The influence of a TNF gene polymorphism on the severity of rheumatoid arthritis in the Brazilian Amazon. Cytokine 61(2):406–412

    Article  CAS  PubMed  Google Scholar 

  8. You CG, Li XJ, Li YM, Wang LP, Li FF, Guo XL et al (2013) Association analysis of single nucleotide polymorphisms of proinflammatory cytokine and their receptors genes with rheumatoid arthritis in northwest Chinese Han population. Cytokine 61(1):133–138

    Article  CAS  PubMed  Google Scholar 

  9. Al-Rayes H, Al-Swailem R, Albelawi M, Arfin M, Al-Asmari A, Tariq M (2011) TNF-alpha and TNF-beta gene polymorphism in Saudi rheumatoid arthritis patients. Clin Med Insights Arthritis Musculoskelet Disord 4:55–63

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Hussein YM, Mohamed RH, Pasha HF, El-Shahawy EE, Alzahrani SS (2011) Association of tumor necrosis factor alpha and its receptor polymorphisms with rheumatoid arthritis in female patients. Cell Immunol 271(1):192–196

    Article  CAS  PubMed  Google Scholar 

  11. Emonts M, Hazes MJ, Houwing-Duistermaat JJ, van der Gaast-de Jongh CE, de Vogel L, Han HK et al (2011) Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study. BMC Med Genet 12:36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Trajkov D, Mishevska-Perchinkova S, Karadzova-Stojanoska A, Petlichkovski A, Strezova A, Spiroski M (2009) Association of 22 cytokine gene polymorphisms with rheumatoid arthritis in population of ethnic Macedonians. Clin Rheumatol 28(11):1291–1300

    Article  PubMed  Google Scholar 

  13. Ates O, Hatemi G, Hamuryudan V, Topal-Sarikaya A (2008) Tumor necrosis factor-alpha and interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients. Clin Rheumatol 27(10):1243–1248

    Article  PubMed  Google Scholar 

  14. Rezaieyazdi Z, Afshari JT, Sandooghi M, Mohajer F (2007) Tumour necrosis factor a -308 promoter polymorphism in patients with rheumatoid arthritis. Rheumatol Int 28(2):189–191

    Article  CAS  PubMed  Google Scholar 

  15. Nemec P, Pavkova-Goldbergova M, Stouracova M, Vasku A, Soucek M, Gatterova J (2008) Polymorphism in the tumor necrosis factor-alpha gene promoter is associated with severity of rheumatoid arthritis in the Czech population. Clin Rheumatol 27(1):59–65

    Article  PubMed  Google Scholar 

  16. Rodriguez-Carreon AA, Zuniga J, Hernandez-Pacheco G, Rodriguez-Perez JM, Perez-Hernandez N, Montes de Oca JV et al (2005) Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans. J Autoimmun 24(1):63–68

    Article  CAS  PubMed  Google Scholar 

  17. Correa PA, Gomez LM, Cadena J, Anaya JM (2005) Autoimmunity and tuberculosis: opposite association with TNF polymorphism. J Rheumatol 32(2):219–224

    CAS  PubMed  Google Scholar 

  18. Pawlik A, Florczak M, Ostanek L, Brzosko M, Brzosko I, Szklarz BG (2005) TNF-alpha -308 promoter polymorphism in patients with rheumatoid arthritis. Scand J Rheumatol 34(1):22–26

    CAS  PubMed  Google Scholar 

  19. Balog A, Klausz G, Gal J, Molnar T, Nagy F, Ocsovszky I et al (2004) Investigation of the prognostic value of TNF-alpha gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-alpha production and apoptosis. Pathobiology 71(5):274–280

    Article  CAS  PubMed  Google Scholar 

  20. Cuenca J, Cuchacovich M, Perez C, Ferreira L, Aguirre A, Schiattino I et al (2003) The -308 polymorphism in the tumour necrosis factor (TNF) gene promoter region and ex vivo lipopolysaccharide-induced TNF expression and cytotoxic activity in Chilean patients with rheumatoid arthritis. Rheumatol Oxf 42(2):308–313

    Article  CAS  Google Scholar 

  21. Yen JH, Chen CJ, Tsai WC, Lin CH, Ou TT, Wu CC et al (2001) Tumor necrosis factor promoter polymorphisms in patients with rheumatoid arthritis in Taiwan. J Rheumatol 28(8):1788–1792

    CAS  PubMed  Google Scholar 

  22. van Krugten MV, Huizinga TW, Kaijzel EL, Zanelli E, Drossaers-Bakker KW, van de Linde P et al (1999) Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis. Genes Immun 1(2):91–96

    Article  PubMed  Google Scholar 

  23. Vinasco J, Beraun Y, Nieto A, Fraile A, Mataran L, Pareja E et al (1997) Polymorphism at the TNF loci in rheumatoid arthritis. Tissue Antigens 49(1):74–78

    Article  CAS  PubMed  Google Scholar 

  24. Danis VA, Millington M, Hyland V, Lawford R, Huang Q, Grennan D (1995) Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorphism in rheumatoid arthritis and systemic lupus erythematosus. Dis Markers 12(2):127–133

    CAS  PubMed  Google Scholar 

  25. Fugger L, Morling N, Ryder LP, Georgsen J, Jakobsen BK, Svejgaard A et al (1989) NcoI restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNF alpha) region in four autoimmune diseases. Tissue Antigens 34(1):17–22

    Article  CAS  PubMed  Google Scholar 

  26. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2006) Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27(2):157–161

    Article  CAS  PubMed  Google Scholar 

  27. Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118(2):225–234

    Article  CAS  PubMed  Google Scholar 

  28. Lee YH, Witte T, Momot T, Schmidt RE, Kaufman KM, Harley JB et al (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52(12):3966–3974

    Article  CAS  PubMed  Google Scholar 

  29. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  30. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  32. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S (2010) Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 30(9):1211–1217

    Article  CAS  PubMed  Google Scholar 

  34. Lacki JK, Moser R, Korczowska I, Mackiewicz S, Muller W (2000) TNF-α gene polymorphism does not affect the clinical and radiological outcome of rheumatoid arthritis. Rheumatol Int 19(4):137–140

    Article  CAS  PubMed  Google Scholar 

  35. Miterski B, Drynda S, Boschow G, Klein W, Oppermann J, Kekow J et al (2004) Complex genetic predisposition in adult and juvenile rheumatoid arthritis. BMC Genet 5:2

    Article  PubMed Central  PubMed  Google Scholar 

  36. Mosaad YM, Abdelsalam A, El-Bassiony SR (2011) Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. Int J Immunogenet 38(5):427–433

    Article  CAS  PubMed  Google Scholar 

  37. Maury CP, Liljestrom M, Laiho K, Tiitinen S, Kaarela K, Hurme M (2003) Tumor necrosis factor alpha, its soluble receptor I, and -308 gene promoter polymorphism in patients with rheumatoid arthritis with or without amyloidosis: implications for the pathogenesis of nephropathy and anemia of chronic disease in reactive amyloidosis. Arthritis Rheum 48(11):3068–3076

    Article  CAS  PubMed  Google Scholar 

  38. Cvetkovic JT, Wallberg-Jonsson S, Stegmayr B, Rantapaa-Dahlqvist S, Lefvert AK (2002) Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-α, IL-1β, and IL-1Ra genes. J Rheumatol 29(2):212–219

    CAS  PubMed  Google Scholar 

  39. Moroldo MB, Donnelly P, Saunders J, Glass DN, Giannini EH (1998) Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 41(9):1620–1624

    Article  CAS  PubMed  Google Scholar 

  40. Lee YH, Harley JB, Nath SK (2006) Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 14(3):364–371

    Article  CAS  PubMed  Google Scholar 

  41. Lee YH, Choi SJ, Ji JD, Song GG (2012) CTLA-4 and TNF-α promoter-308 A/G polymorphisms and ANCA-associated vasculitis susceptibility: a meta-analysis. Mol Biol Rep 39(1):319–326

    Article  CAS  PubMed  Google Scholar 

  42. Baena A, Leung JY, Sullivan AD, Landires I, Vasquez-Luna N, Quinones-Berrocal J et al (2002) TNF-α promoter single nucleotide polymorphisms are markers of human ancestry. Genes Immun 3(8):482–487

    Article  CAS  PubMed  Google Scholar 

  43. Lee YH, Ji JD, Song GG (2007) Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis. J Rheumatol 34(1):43–49

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

We have no financial and non-financial conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 ga, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea

    Gwan Gyu Song, Jae-Hoon Kim & Young Ho Lee

  2. The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea

    Sang-Cheol Bae

Authors
  1. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sang-Cheol Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jae-Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, G.G., Bae, SC., Kim, JH. et al. Association between TNF-α promoter –308 A/G polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatol Int 34, 465–471 (2014). https://doi.org/10.1007/s00296-013-2919-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-013-2919-5

Keywords

Search

Navigation