Skip to main content
SpringerLink
Log in

Risk Association Between the NF-κB1 -94ins/delATTG Promoter Polymorphism and Inflammatory Bowel Diseases: A Meta-Analysis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Extensive investigation of the NF-κB1 -94ins/delATTG promoter polymorphism for risk association with ulcerative colitis (UC) and Crohn’s disease (CD) risk has yielded conflicting results.

Aims

The objective of this meta-analysis was to evaluate the risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and UC and CD.

Methods

All eligible case–control studies of the association of NF-κB1 -94ins/delATTG promoter polymorphism with UC and CD were identified in the Pubmed and Embase databases. From these data, odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Meta-analysis was performed for alleles (D vs. W) and genotypes (DD + WD vs. WW, DD vs. WW + WD, DD vs. WW, WD vs. WW) in a fixed/random effects model.

Results

Nine case–control studies that included 4,447 cases (2,631 UC and 1,816 CD) and 2,195 controls were identified. Results indicated increased risk association of D allele carriers with UC (D vs. W: OR = 1.08, 95 % CI = 1.01–1.17, P = 0.03; DD vs. WW + WD: OR = 1.16, 95 % CI = 1.01–1.32, P = 0.04 and DD vs. WW: OR = 1.20, 95 % CI = 1.03–1.39, P = 0.02). No risk association was identified with CD.

Conclusion

This meta-analysis indicated that the NF-κB1 -94ins/delATTG promoter polymorphism is a risk factor for UC but not CD.

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

Similar content being viewed by others

References

  1. Bonen DK, Cho JH. The genetics of inflammatory bowel disease. Gastroenterology. 2003;124:524–536.

    Google Scholar 

  2. De Vry CG, Prasad S, Komuves L, et al. Non-viral delivery of nuclear factor-kappaB decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis. Gut. 2007;56:524–533.

    Article  PubMed  Google Scholar 

  3. Takedatsu H, Taylor KD, Mei L, et al. Linkage of Crohn’s disease-related serological phenotypes: NF-κB1 haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF-kappaB activation. Gut. 2009;58:60–67.

    Article  PubMed  CAS  Google Scholar 

  4. Le Beau MM, Ito C, Cogswell P, Espinosa R 3rd, Fernald AA, Baldwin AS Jr. Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NF-κB2) and the I kappa B/MAD-3 (NF-κBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively. Genomics. 1992;14:529–531.

    Article  PubMed  Google Scholar 

  5. Mathew S, Murty VV, Dalla-Favera R, Chaganti RS. Chromosomal localization of genes encoding the transcription factors, c-rel, NF-kappa Bp50, NF-kappa Bp65, and lyt-10 by fluorescence in situ hybridization. Oncogene. 1993;8:191–193.

    PubMed  CAS  Google Scholar 

  6. Beinke S, Ley SC. Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology. Biochem J. 2004;382:393–409.

    Article  PubMed  CAS  Google Scholar 

  7. Karban AS, Okazaki T, Panhuysen CI, et al. Functional annotation of a novel NF-κB1 promoter polymorphism that increases risk for ulcerative colitis. Hum Mol Genet. 2004;13:35–45.

    Article  PubMed  CAS  Google Scholar 

  8. Borm ME, van Bodegraven AA, Mulder CJ, Kraal G, Bouma G. A NF-κB1 promoter polymorphism is involved in susceptibility to ulcerative colitis. Int J Immunogenet. 2005;32:401–405.

    Article  PubMed  CAS  Google Scholar 

  9. Oliver J, Gómez-García M, Paco L, et al. A functional polymorphism of the NF-κB1 promoter is not associated with ulcerative colitis in a Spanish population. Inflamm Bowel Dis. 2005;11:576–579.

    Article  PubMed  Google Scholar 

  10. Mirza MM, Fisher SA, Onnie C, et al. No association of the NF-κB1 promoter polymorphism with ulcerative colitis in a British case control cohort. Gut. 2005;54:1205–1206.

    Article  PubMed  CAS  Google Scholar 

  11. Glas J, Török HP, Tonenchi L, et al. Role of the NF-κB1-94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes. Inflamm Bowel Dis. 2006;12:606–611.

    Article  PubMed  Google Scholar 

  12. Latiano A, Palmieri O, Valvano MR, et al. Evaluating the role of the genetic variations of PTPN22, NF-κB1, and FcGRIIIA genes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis. 2007;13:1212–1219.

    Article  PubMed  Google Scholar 

  13. Szamosi T, Lakatos PL, Hungarian IBD Study Group, et al. The 3′UTR NF-κBIA variant is associated with extensive colitis in Hungarian IBD patients. Dig Dis Sci. 2009;54:351–359.

    Article  PubMed  CAS  Google Scholar 

  14. Lei Y, Deng C-S. Association of NF-κB1 -94ins/delATTG promoter polymorphism with ulcerative colitis in Chinese Han population of Hubei Province. World Chin J Digestol. 2009;17:2212–2216.

    CAS  Google Scholar 

  15. Andersen V, Christensen J, Ernst A, et al. Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease. World J Gastroenterol. 2011;17:197–206.

    Article  PubMed  CAS  Google Scholar 

  16. Zou YF, Wang F, Feng XL, et al. Association of NF-κB1 -94ins/delATTG promoter polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis. Tissue Antigens. 2011;77:9–17.

    Article  PubMed  CAS  Google Scholar 

  17. Zou YF, Yuan FL, Feng XL, et al. Association between NF-κB1 -94ins/delATTG promoter polymorphism and cancer risk: a meta-analysis. Cancer Invest. 2011;29:78–85.

    Article  PubMed  CAS  Google Scholar 

  18. Andersen V, Christensen J, Østergaard M et al. Association of the nuclear receptors PXR, LXR and PPARγ with ulcerative colitis in the Danish population: a case-control study. Inflamm Bowel Dis. 2009;15:S29.

    Google Scholar 

  19. Borm ME, He J, Kelsall B, Peña AS, Strober W, Bouma G. A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models. Gastroenterology. 2005;128:74–85.

    Article  PubMed  CAS  Google Scholar 

  20. Farmer MA, Sundberg JP, Bristol IJ, et al. A major quantitative trait locus on chromosome 3 controls colitis severity in IL-10-deficient mice. Proc Natl Acad Sci USA. 2001;98:13820–13825.

    Article  PubMed  CAS  Google Scholar 

  21. Chang M, Lee AJ, Fitzpatrick L, Zhang M, Sun SC. NF-kappaB1 p105 regulates T cell homeostasis and prevents chronic inflammation. J Immunol. 2009;182:3131–3138.

    Article  PubMed  CAS  Google Scholar 

  22. Tomczak MF, Erdman SE, Poutahidis T, et al. NF-kappa B is required within the innate immune system to inhibit microflora-induced colitis and expression of IL-12 p40. J Immunol. 2003;171:1484–1492.

    PubMed  CAS  Google Scholar 

  23. Hampe J, Schreiber S, Shaw SH, et al. A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. Am J Hum Genet. 1999;64:808–816.

    Article  PubMed  CAS  Google Scholar 

  24. Cho JH, Nicolae DL, Gold LH, et al. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1. Proc Natl Acad Sci USA. 1998;95:7502–7507.

    Article  PubMed  CAS  Google Scholar 

  25. Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med. 2008;263:591–596.

    Article  PubMed  CAS  Google Scholar 

  26. Ishikawa H, Claudio E, Dambach D, Raventós-Suárez C, Ryan C, Bravo R. Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-κB1) but expressing p50. J Exp Med. 1998;187:985–996.

    Article  PubMed  CAS  Google Scholar 

  27. Erdman S, Fox JG, Dangler CA, Feldman D, Horwitz BH. Typhlocolitis in NF-kappa B-deficient mice. J Immunol. 2001;166:1443–1447.

    PubMed  CAS  Google Scholar 

  28. Baer M, Dillner A, Schwartz RC, Sedon C, Nedospasov S, Johnson PF. Tumor necrosis factor alpha transcription in macrophages is attenuated by an autocrine factor that preferentially induces NF-kappaB p50. Mol Cell Biol. 1998;18:5678–5689.

    PubMed  CAS  Google Scholar 

  29. Visekruna A, Joeris T, Seidel D, et al. Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. J Clin Invest. 2006;116:3195–3203.

    Article  PubMed  CAS  Google Scholar 

  30. Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ. Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin Exp Immunol. 2004;135:64–73.

    Article  PubMed  CAS  Google Scholar 

  31. Tomczak MF, Erdman SE, Davidson A, et al. Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B. J Immunol. 2006;177:7332–7339.

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Meilan Liang, Xinyu Xu, Yaoyao Gong, Yurong Tang & Lin Lin

Authors
  1. Meilan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinyu Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaoyao Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yurong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, M., Xu, X., Gong, Y. et al. Risk Association Between the NF-κB1 -94ins/delATTG Promoter Polymorphism and Inflammatory Bowel Diseases: A Meta-Analysis. Dig Dis Sci 57, 2304–2309 (2012). https://doi.org/10.1007/s10620-012-2164-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2164-x

Keywords

Search

Navigation