The Toll-Like Receptor 4 D299G and T399I Polymorphisms Are Associated with Crohn’s Disease and Ulcerative Colitis: A Meta-Analysis

Abstract

Background: Some studies have reported that Toll-like receptor 4 (TLR4) D299G and T399I polymorphisms are associated with increased Crohn’s disease (CD) and ulcerative colitis (UC) risk in the Caucasian population. However, the results have been inconsistent. Methods: A systemic review of the published data (16 studies with 8,387 cases and 7,013 controls for D299G; 8 studies with 3,881 cases and 1,861 controls for T399I) was undertaken and a meta-analysis was performed to test whether TLR4 D299G and T399I polymorphisms were associated with CD or UC susceptibility and whether 299Gly carriage was associated with phenotypes of CD patients. Results: The TLR4 299Gly allele showed a significant association with CD and UC in the Caucasian population (OR 1.29, 95% CI 1.08–1.54, and OR 1.28, 95% CI 1.08–1.51, respectively). Similar association was detected between the T399I polymorphism and susceptibility to CD and UC (OR 1.37, 95% CI 1.12–1.68, and OR 1.46, 95% CI 1.13–1.88, respectively). However, no significant association was identified between CD phenotypes and 299Gly carriage. Conclusion: The meta-analysis showed that TLR4 D299G and T399I confer a significant risk for developing CD and UC in Caucasians. Additional well-powered studies of the association between TLR4 variants and UC are needed.

Association between Toll-Like Receptor 4 T399I Gene Polymorphism and the Susceptibility to Crohn’s Disease: A Meta-Analysis of Case-Control Studies

“…Contrary to meta-analysis reported by Shen et al [39], our current study suggested that the TLR4 T399I polymorphism might not be associated with CD susceptibility in Caucasians, while moderate association was observed in Asians. Some differences exist between our analysis and other meta-analysis.…”

Role of Gut Microbiota in a Zebrafish Model with Chemically Induced Enterocolitis Involving Toll-Like Receptor Signaling Pathways

“…8,9 Moreover, a meta-analysis revealed that genetic variations in TLR4 conferred a statistically significant risk of developing CD and UC. 10 In addition to TLR4, polymorphisms in TLR2, the main receptor for gram-positive bacteria, have been associated with IBD in humans and there is an inflammation-dependent induction of TLR2 expression in intestinal macrophages. 11,12 On activation of the TLRs, different adaptor proteins, including MyD88, Mal (TIRAP), TRIF (TICAM), TRAM, (TICAM2), or SARM are recruited, and they trigger a signaling pathway, leading to the subsequent downstream activation of signals such as transcription factor NF-jB (nuclear factor-jB), which are responsible for induction of pro-inflammatory cytokines and chemokines.…”

Toll-like receptor 4 polymorphisms and susceptibility to multiple autoimmune diseases: evidence based on pooled analysis

“…Previous meta-analysis indicated that TLR4 polymorphisms appeared to be correlated with Crohn's disease, ulcerative colitis [8], vasculitis [9] and cancer [10], but not with sepsis [11], rheumatoid arthritis, ankylosing spondylitis [12][13][14], and atherosclerosis [15]. In the present study, we performed a systematic review of the association between TLR4 Asp299Gly and Thr399Ile polymorphisms and the risk of ADs.…”

“…In fact, in previous meta-analyses TLR4 polymorphisms appeared to be correlated with Crohn's disease, ulcerative colitis [8], vasculitis [9] and cancer [10], but not with sepsis [11], rheumatoid arthritis, ankylosing spondylitis [12][13][14], and atherosclerosis [15]. To date, a number of molecular epidemiological studies have been done to evaluate the association between TLR4 Asp299Gly and Thr399Ile polymorphisms and several autoimmune diseases (ADs) including type 1 diabetes (T1DM) [16], celiac disease (CED) [16, DOI: 10.5114/ceji.2013.37757 17], rheumatoid arthritis (RA) [18][19][20][21], multiple sclerosis (MS) [22,23], and systemic lupus erythematosus (SLE) [19] in Caucasians.…”