One SNP (rs4986791 in the TLR-4 locus) and 2 SNPs (rs6785049 in the Pregnane-x-receptor gene and rs10500264 in the SLCA10 gene) were associated with a change in albumin and hemoglobin over time respectively in our IBD cohort.
The TLR4-Thr399Ile variant was strongly associated with susceptibility to IBD, whereas TLR4-Asp299Gly seems to play a role in the clinical expression of UC.
However, meta-analysis demonstrated significantly higher frequencies of both Asp299Gly and Thr399Ile SNPs in IBD and CD and for 399Ileu carriage in UC patients.
The TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp polymorphisms may not be associated with IBD in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.
No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P > 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P > 0.05).
Two commonly occurring SNPs in the human TLR4 gene (Asp299Gly and Thr399Ile) have been shown to be associated with increased risk of Gram-negative bacteremia in sepsis patients and with susceptibility to inflammatory bowel disease.
The Asp299Gly and Thr399Ile variants do not show an association with CD, UC, or IBD as a group, indicating that these polymorphisms are likely not the causal ones.