Skip to main content
SpringerLink
Log in

Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 −1082G/A, −819C/T and −592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy–Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism −1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004–1.627) and 1.238 (1.027–1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the −819C/T polymorphism were at increased risk of IBD (OR 1.093, 95 % CI 1.004–1.190). Association with the −819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95 % CI 1.010–1.206; CC + CT vs. TT: OR 1.328, 95 % CI 1.006–1.754; CC vs. TT: OR 1.339, 95 % CI 1.008–1.778), and with UC (CC vs. CT + TT: OR 1.188, 95 % CI 1.019–1.385). No significant association was found between the −592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms −1082G/A and −819C/T and the risk of IBD.

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. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369(9573):40–1627

    Google Scholar 

  2. Kappelman MD et al (2007) The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 5(12):9–1424

    Google Scholar 

  3. Lakatos PL (2006) Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J Gastroenterol 12(38):8–6102

    Google Scholar 

  4. Wang YF, Ouyang Q, Hu RW (2010) Progression of inflammatory bowel disease in China. J Dig Dis 11(2):76–82

    Article  PubMed  Google Scholar 

  5. Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361(21):78–2066

    Article  Google Scholar 

  6. Turner DM et al (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24(1):1–8

    Article  CAS  PubMed  Google Scholar 

  7. Kuhn R et al (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):74–263

    Article  Google Scholar 

  8. Amre DK et al (2009) Interleukin 10 (IL-10) gene variants and susceptibility for paediatric onset Crohn’s disease. Aliment Pharmacol Ther 29(9):31–1025

    Article  Google Scholar 

  9. Garza-Gonzalez E et al (2010) Genetic risk factors for inflammatory bowel disease in a North-eastern Mexican population. Int J Immunogenet 37(5):9–355

    Article  Google Scholar 

  10. Tedde A et al (2008) Interleukin-10 promoter polymorphisms influence susceptibility to ulcerative colitis in a gender-specific manner. Scand J Gastroenterol 43(6):8–712

    Article  Google Scholar 

  11. Howell WM, Rose-Zerilli MJ (2007) Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutr 137(1 Suppl):194S–199S

    CAS  PubMed  Google Scholar 

  12. Crawley E et al (1999) Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 42(6):8–1101

    Article  Google Scholar 

  13. Hoffmann SC et al (2001) Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 72(8):50–1444

    Article  Google Scholar 

  14. Reuss E et al (2002) Differential regulation of interleukin-10 production by genetic and environmental factors–a twin study. Genes Immun 3(7):13–407

    Article  Google Scholar 

  15. Ahirwar DK et al (2011) Role of tumor necrosis factor-alpha (C-863A) polymorphism in pathogenesis of inflammatory bowel disease in Northern India. J Gastrointest Cancer 42(3):149–154

    Article  Google Scholar 

  16. Andersen V et al (2010) The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study. BMC Med Genet 11:82

    Article  PubMed Central  PubMed  Google Scholar 

  17. Balding J et al (2004) Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms. Mediators Inflamm 13(3):7–181

    Article  Google Scholar 

  18. Cantor MJ, Nickerson P, Bernstein CN (2005) The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol 100(5):42–1134

    Article  Google Scholar 

  19. Castro-Santos P et al (2006) TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency. Am J Gastroenterol 101(5):47–1039

    Article  Google Scholar 

  20. Celik Y et al (2006) Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease. Scand J Gastroenterol 41(5):65–559

    Article  Google Scholar 

  21. Fernandez L et al (2005) Interleukin-10 polymorphisms in Spanish patients with IBD. Inflamm Bowel Dis 11(8):43–739

    Article  Google Scholar 

  22. Hong J et al (2008) IL4, IL10, IL16, and TNF polymorphisms in New Zealand Caucasian Crohn’s disease patients. Int J Colorectal Dis 23(3):7–335

    Article  Google Scholar 

  23. Klausz G et al (2005) Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn’s disease. Scand J Gastroenterol 40(10):204–1197

    Article  Google Scholar 

  24. Klein W et al (2000) The IL-10 gene is not involved in the predisposition to inflammatory bowel disease. Electrophoresis 21(17):82–3578

    Article  Google Scholar 

  25. Koss K et al (2000) Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun 1(3):90–185

    Google Scholar 

  26. Sanchez R et al (2009) IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn’s disease location. World J Gastroenterol 15(30):82–3776

    Article  Google Scholar 

  27. Tagore A et al (1999) Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Tissue Antigens 54(4):90–386

    Article  Google Scholar 

  28. Wang AH et al (2011) The effect of IL-10 genetic variation and interleukin 10 serum levels on Crohn’s disease susceptibility in a New Zealand population. Hum Immunol 72(5):5–431

    CAS  Google Scholar 

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

    Article  Google Scholar 

  30. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):58–1539

    Article  Google Scholar 

  31. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):7–1533

    Article  Google Scholar 

  32. Egger M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):34–629

    Article  Google Scholar 

  33. Clark MF, Baudouin SV (2006) A systematic review of the quality of genetic association studies in human sepsis. Intensive Care Med 32(11):12–1706

    Article  Google Scholar 

  34. Srivastava K et al (2011) Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutat Res 728(1–2):67–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Ioannidis JP et al (2008) Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37(1):32–120

    Article  Google Scholar 

  36. Glocker EO et al (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med 361(21):45–2033

    Article  Google Scholar 

  37. van der Linde K et al (2003) A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease. Scand J Gastroenterol 38(6):7–611

    Google Scholar 

  38. Parkes M, Satsangi J, Jewell D (1998) Contribution of the IL-2 and IL-10 genes to inflammatory bowel disease (IBD) susceptibility. Clin Exp Immunol 113(1):28–32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Juyal G et al (2011) An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians. PLoS One 6(1):e16565

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Festen EA et al (2010) Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk. Am J Gastroenterol 105(2):395–402

    Article  CAS  PubMed  Google Scholar 

  41. Shi J et al (2011) Haplotype-based analysis of ulcerative colitis risk loci identifies both IL2 and IL21 as susceptibility genes in Han Chinese. Inflamm Bowel Dis 17(12):9–2472

    Article  Google Scholar 

  42. Ghaith OA et al (2010) Lack of correlation between IL-10R1 S138G loss-of-function allele and IBD in the Lebanese population. Inflamm Bowel Dis 16(11):20–1819

    Article  Google Scholar 

  43. Grundtner P et al (2009) The IL-10R1 S138G loss-of-function allele and ulcerative colitis. Genes Immun 10(1):84–92

    Article  CAS  PubMed  Google Scholar 

  44. Gasche C et al (2003) Novel variants of the IL-10 receptor 1 affect inhibition of monocyte TNF-alpha production. J Immunol 170(11):82–5578

    Google Scholar 

  45. Aithal GP et al (2001) Role of polymorphisms in the interleukin-10 gene in determining disease susceptibility and phenotype in inflamatory bowel disease. Dig Dis Sci 46(7):5–1520

    Article  Google Scholar 

  46. Moran CJ et al (2012) IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis 19(1):115–123

    Article  Google Scholar 

  47. Marcuzzi A et al (2012) Inflammation profile of four early onset Crohn patients. Gene 493(2):5–282

    Article  Google Scholar 

  48. Gasche C et al (2011) IL-10RA truncation mutations and Semite populations. Inflamm Bowel Dis 17(6):1438

    Article  PubMed  Google Scholar 

  49. Bernstein CN et al (2006) A population-based case control study of potential risk factors for IBD. Am J Gastroenterol 101(5):993–1002

    Article  PubMed  Google Scholar 

  50. Hugot JP et al (1999) Etiology of the inflammatory bowel diseases. Int J Colorectal Dis 14(1):2–9

    Article  CAS  PubMed  Google Scholar 

  51. Barbara G et al (2000) Interleukin 10 gene transfer prevents experimental colitis in rats. Gut 46(3):344–349

    Article  CAS  PubMed  Google Scholar 

  52. van Deventer SJ, Elson CO, Fedorak RN (1997) Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Crohn’s Disease Study Group. Gastroenterology 113(2):383–389

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (Grant Nos. 81172842, 31200934, 61300116) and the Natural Science Foundation of Heilongjiang Province (Grant No. C201206).

Author information

Authors and Affiliations

  1. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, People’s Republic of China

    Hongchao Lv, Yongshuai Jiang, Jin Li, Mingming Zhang, Zhenwei Shang, Jiajia Zheng, Xin Wu, Panpan Liu & Ruijie Zhang

  2. Chinese Medicine Department of The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China

    Huimin Yu

  3. The Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, Heilongjiang, People’s Republic of China

    Hongchao Lv, Yongshuai Jiang, Jin Li, Mingming Zhang, Zhenwei Shang, Jiajia Zheng, Xin Wu, Panpan Liu, Ruijie Zhang & Huimin Yu

Authors
  1. Hongchao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongshuai Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mingming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenwei Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiajia Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Panpan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ruijie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huimin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xin Wu, Ruijie Zhang or Huimin Yu.

Additional information

Hongchao Lv, Yongshuai Jiang and Ruijie Zhang are joint first authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 226 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lv, H., Jiang, Y., Li, J. et al. Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease. Mol Biol Rep 41, 1299–1310 (2014). https://doi.org/10.1007/s11033-013-2975-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2975-7

Keywords

Search

Navigation