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Digestion. 2010;81(2):69-77. doi: 10.1159/000260417. Epub 2010 Jan 9.

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

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



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.


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.


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.


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.

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