Immunologic Research

, Volume 67, Issue 1, pp 142–150 | Cite as

Correlations between TLR polymorphisms and inflammatory bowel disease: a meta-analysis of 49 case-control studies

  • Huijuan WangEmail author
  • Shuhong Zhou
  • Jiahong Zhang
  • Shangwen Lei
  • Jing Zhou
Original Article


Recently, the roles of toll-like receptor (TLR) polymorphisms in inflammatory bowel disease (IBD) were intensively explored, with conflicting results. Therefore, we performed this study to better assess the relationship between TLR polymorphisms and the risk of IBD. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate associations between TLR polymorphisms and IBD. Significant associations with the risk of IBD were detected for the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms were significantly associated with the risk of IBD in Caucasians. Moreover, the TLR4 rs4986790 polymorphism was significantly correlated with the risk of IBD in West Asians, while the TLR9 rs352140 polymorphism was significantly associated with the risk of IBD in Africans. When we stratified available data according to type of disease, we found similar positive results for TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms. Our findings indicate that TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms may serve as genetic biomarkers of IBD in certain ethnicities. However, further well-designed studies are still warranted to confirm our findings.


Toll-like receptor (TLRGene polymorphisms Inflammatory bowel disease (IBD) Crohn’s disease (CD) Ulcerative colitis (UC) Meta-analysis 


Authors’ contributions

Huijuan Wang and Shuhong Zhou conceived of the study and participated in its design. Huijuan Wang and Shuhong Zhou conducted the systematic literature review. Jiahong Zhang, Shangwen Lei, and Jing Zhou performed data analyses. Huijuan Wang and Shuhong Zhou drafted the manuscript. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Informed consent

For this type of study formal consent is not required.


  1. 1.
    Burisch J, Munkholm P. The epidemiology of inflammatory bowel disease. Scand J Gastroenterol. 2015;50:942–51.CrossRefGoogle Scholar
  2. 2.
    Bouguen G, Chevaux JB, Peyrin-Biroulet L. Recent advances in cytokines: therapeutic implications for inflammatory bowel diseases. World J Gastroenterol. 2011;17:547–56.CrossRefGoogle Scholar
  3. 3.
    Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14:329–42.CrossRefGoogle Scholar
  4. 4.
    Mitsuyama K, Niwa M, Takedatsu H, Yamasaki H, Kuwaki K, Yoshioka S, et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol. 2016;22:1304–10.CrossRefGoogle Scholar
  5. 5.
    Ko JK, Auyeung KK. Inflammatory bowel disease: etiology, pathogenesis and current therapy. Curr Pharm Des. 2014;20:1082–96.CrossRefGoogle Scholar
  6. 6.
    Altwegg R, Vincent T. TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease. Mediat Inflamm. 2014;2014:172821.CrossRefGoogle Scholar
  7. 7.
    West AP, Koblansky AA, Ghosh S. Recognition and signaling by toll-like receptors. Annu Rev Cell Dev Biol. 2006;22:409–37.CrossRefGoogle Scholar
  8. 8.
    De Nardo D. Toll-like receptors: activation, signalling and transcriptional modulation. Cytokine. 2015;74:181–9.CrossRefGoogle Scholar
  9. 9.
    Kim EJ, Chung WC, Lee KM, Paik CN, Jung SH, Lee BI, et al. Association between toll-like receptors/CD14 gene polymorphisms and inflammatory bowel disease in Korean population. J Korean Med Sci. 2012;27:72–7.CrossRefGoogle Scholar
  10. 10.
    Chen L, Lin MJ, Zhan LL, Lv XP. Analysis of TLR4 and TLR2 polymorphisms in inflammatory bowel disease in a Guangxi Zhuang population. World J Gastroenterol. 2012;18:6856–60.CrossRefGoogle Scholar
  11. 11.
    Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, et al. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis. 2006;12:1–8.CrossRefGoogle Scholar
  12. 12.
    Abad C, González-Escribano MF, Diaz-Gallo LM, Lucena-Soto JM, Márquez JL, Leo E, et al. Association of Toll-like receptor 10 and susceptibility to Crohn’s disease independent of NOD2. Genes Immun. 2011;12:635–42.CrossRefGoogle Scholar
  13. 13.
    Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefGoogle Scholar
  14. 14.
    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.CrossRefGoogle Scholar
  15. 15.
    Bernstein CN. Treatment of IBD: where we are and where we are going. Am J Gastroenterol. 2015;110:114–26.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Huijuan Wang
    • 1
    Email author
  • Shuhong Zhou
    • 1
  • Jiahong Zhang
    • 1
  • Shangwen Lei
    • 1
  • Jing Zhou
    • 1
  1. 1.Department of Immunology and RheumatologyGansu Provincial HospitalLanzhouChina

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