The Toll-like receptor 4 D299G and T399I polymorphisms are associated with Crohn's disease and ulcerative colitis: a meta-analysis

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.