Skip to main content
SpringerLink
Log in

Association of TNF-α promoter-308 A/G polymorphism with susceptibility to systemic lupus erythematosus: a meta-analysis

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

Abstract

Published data on the association between tumor necrosis factor-alpha (TNF-α) promoter-308 A/G polymorphism and systemic lupus erythematosus (SLE) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 28 studies including 2,992 cases and 4,326 controls (5,924 cases and 8,484 controls in A versus G comparison) were involved in this meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. In addition, we also performed a “model-free” analysis by considering the G/G genotype as the reference and estimated the OR for the A/A versus G/G and A/G versus G/G genotype. Overall, an association of TNF-α promoter-308 A/G polymorphism with SLE was found (A versus G: OR = 1.686, 95% CI = 1.400–2.032, P < 0.001; A/A versus A/G+G/G: OR = 3.043, 95% CI = 2.185–4.238, P < 0.001; A/A+A/G versus G/G: OR = 1.822, 95% CI = 1.379–2.407, P < 0.001; A/A versus G/G: OR = 3.686, 95% CI = 2.628–5.172, P < 0.001; A/G versus G/G: OR = 1.691, 95% CI = 1.291–2.215, P < 0.001). However, stratification by ethnicity indicated that the risk A allele was not associated with SLE in Asian (A versus G: OR = 1.207, 95% CI = 0.856–1.702, P = 0.283) and African population (A versus G: OR = 1.225, 95% CI = 0.597–2.516, P = 0.580). In summary, this meta-analysis indicated that TNF-α promoter-308-A/G polymorphism is associated with susceptibility to SLE.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Criswell LA, Pfeiffer KA, Lum RF et al (2005) Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620 W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 76:561–571

    Article  PubMed  CAS  Google Scholar 

  2. Vassalli P (1992) The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10:411–452

    Article  PubMed  CAS  Google Scholar 

  3. Dunham I, Sargent CA, Trowsdale J et al (1987) Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci USA 84:7237–7241

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Egger M, Davey SG, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634

    Article  CAS  Google Scholar 

  6. McHugh NJ, Owen P, Cox B et al (2006) MHC class II, tumour necrosis factor a, and lymphotoxin a gene haplotype associations with serological subsets of systemic lupus erythematosus. Ann Rheum Dis 65:488–494

    Article  PubMed  CAS  Google Scholar 

  7. Hrycek A, Siekiera U, Cieślik P et al (2005) HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 26:1–6

    Article  PubMed  CAS  Google Scholar 

  8. Suárez A, López P, Mozo L et al (2005) Differential effect of IL10 and TNFa genotypes on determining susceptibility to discoid and systemic lupus erythematosus. Ann Rheum Dis 64:1605–1610

    Article  PubMed  Google Scholar 

  9. Schotte H, Willeke P, Tidow N et al (2005) Extended haplotype analysis reveals an association of TNF polymorphisms with susceptibility to systemic lupus erythematosus beyond HLA-DR3. Scand J Rheumatol 34:114–121

    Article  PubMed  CAS  Google Scholar 

  10. Parks CG, Pandey JP, Dooley MA et al (2004) Genetic polymorphisms in tumor necrosis factor (TNF)-alpha and TNF-beta in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1alpha-889 C/T polymorphism. Hum Immunol 65:622–631

    Article  PubMed  CAS  Google Scholar 

  11. May LA, Huang Q, Morris D et al (2002) Relationship of tumour necrosis factor alpha gene polymorphisms and neuropsychiatric lupus. Lupus 11:114–118

    Article  PubMed  CAS  Google Scholar 

  12. van der Linden MW, van der Slik AR, Zanelli E et al (2001) Six microsatellite markers on the short arm of chromosome 6 in relation to HLA-DR3 and TNF-308A in systemic lupus erythematosus. Genes Immun 2:373–380

    Article  PubMed  Google Scholar 

  13. Rood MJ, van Krugten MV, Zanelli E et al (2000) TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus. Arthritis Rheum 43:129–134

    Article  PubMed  CAS  Google Scholar 

  14. Rudwaleit M, Tikly M, Khamashta M et al (1996) Interethnic differences in the association of tumor necrosis factor promoter polymorphisms with systemic lupus erythematosus. J Rheumatol 23:1725–1728

    PubMed  CAS  Google Scholar 

  15. D’Alfonso S, Colombo G, Della BS et al (1996) Association between polymorphisms in the TNF region and systemic lupus erythematosus in the Italian population. Tissue Antigens 47:551–555

    Article  PubMed  Google Scholar 

  16. Danis VA, Millington M, Hyland V et al (1995) Increased frequency of the uncommon allele of a tumour necrosis factor alpha gene polymorphism in rheumatoid arthritis and systemic lupus erythematosus. Dis Markers 12:127–133

    PubMed  CAS  Google Scholar 

  17. Wilson AG, Gordon C, di Giovine FS et al (1994) A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha. Eur J Immunol 24:191–195

    Article  PubMed  CAS  Google Scholar 

  18. Goldstein R, Sengar DP (1993) Comparative studies of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with systemic lupus erythematosus. Arthritis Rheum 36:1121–1127

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Lin YJ, Chen RH, Wan L et al (2009) Association of TNF-α gene polymorphisms with systemic lupus erythematosus in Taiwanese patients. Lupus 18:974–979

    Article  PubMed  Google Scholar 

  21. Hirankarn N, Avihingsanon Y, Wongpiyabovorn J (2007) Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism -863, but not -308 and -238, in Thai population. Int J Immunogenet 34:425–430

    Article  PubMed  CAS  Google Scholar 

  22. Azizah MR, Kuak SH, Ainol SS et al (2004) Association of the tumor necrosis factor alpha gene polymorphism with susceptibility and clinical-immunological findings of systemic lupus erythematosus. Asian Pac J Allergy Immunol 22:159–163

    PubMed  CAS  Google Scholar 

  23. Wang M, Dong Y, Huang S (1999) Study on the association between tumor necrosis factor alpha gene polymorphism and systemic lupus erythematosus. Zhonghua Nei Ke Za Zhi 38:393–396

    PubMed  CAS  Google Scholar 

  24. Wang Y, Zhang Y, Zhu S (1998) The association of susceptibility of SLE and the gene polymorphism of TNF. Zhonghua Yi Xue Za Zhi 78:111–114

    PubMed  CAS  Google Scholar 

  25. Chen CJ, Yen JH, Tsai WC et al (1997) The TNF2 allele does not contribute towards susceptibility to systemic lupus erythematosus. Immunol Lett 55:1–3

    Article  PubMed  CAS  Google Scholar 

  26. Fong KY, Howe HS, Tin SK et al (1996) Polymorphism of the regulatory region of tumour necrosis factor alpha gene in patients with systemic lupus erythematosus. Ann Acad Med Singapore 25:90–93

    PubMed  CAS  Google Scholar 

  27. Tomita Y, Hashimoto S, Yamagami K et al (1993) Restriction fragment length polymorphism (RFLP) analysis in the TNF genes of patients with systemic lupus erythematosus (SLE). Clin Exp Rheumatol 11:533–536

    PubMed  CAS  Google Scholar 

  28. Atsumi T (1992) Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by restriction fragment length polymorphism and production by peripheral blood mononuclear cells. Hokkaido Igaku Zasshi 67:408–419

    PubMed  CAS  Google Scholar 

  29. Sullivan KE, Wooten C, Schmeckpeper BJ et al (1997) A promoter polymorphism of tumor necrosis factor alpha associated with systemic lupus erythematosus in African–Americans. Arthritis Rheum 40:2207–2211

    Article  PubMed  CAS  Google Scholar 

  30. Guarnizo-Zuccardi P, Lopez Y, Giraldo M et al (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70:376–382

    Article  PubMed  CAS  Google Scholar 

  31. Correa P, Gomez ML, Cadena J et al (2005) Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. J Rheumatol 32:219–224

    PubMed  CAS  Google Scholar 

  32. Jiménez-Morales S, Velázquez-Cruz R, Ramírez-Bello J et al (2009) Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric population. Hum Immunol 70:251–256

    Article  PubMed  Google Scholar 

  33. Zuniga J, Vargas-Alarcon G, Hernandez-Pacheco G et al (2001) Tumor necrosis factoralpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). Genes Immun 2:363–366

    Article  PubMed  CAS  Google Scholar 

  34. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  35. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a metaanalysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  36. Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  37. Lee YH, Rho YH, Choi SJ et al (2007) The PTPN22 C1858T functional polymorphism and autoimmune diseases—a meta-analysis. Rheumatology 46:49–56

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the key program of National Natural Science Foundation of China (30830089, 30771848) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (20070366002).

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, People’s Republic of China

    Hai-Feng Pan, Rui-Xue Leng, Chao Wang, Wei-Zi Qin, Li-Li Chen, Zhen-Qiu Zha, Jin-Hui Tao & Dong-Qing Ye

  2. Department of Rheumatology, Anhui Provincial Hospital, 17 Lujiang Road, 230001, Hefei, Anhui, People’s Republic of China

    Jin-Hui Tao

Authors
  1. Hai-Feng Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui-Xue Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei-Zi Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhen-Qiu Zha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin-Hui Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong-Qing Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong-Qing Ye.

Additional information

Hai-Feng Pan, and Rui-Xue Leng contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, HF., Leng, RX., Wang, C. et al. Association of TNF-α promoter-308 A/G polymorphism with susceptibility to systemic lupus erythematosus: a meta-analysis. Rheumatol Int 32, 2083–2092 (2012). https://doi.org/10.1007/s00296-011-1924-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-011-1924-9

Keywords

Search

Navigation