Single Nucleotide Polymorphism in TLR4 Promoter and its Effect on Protein Expression

Objective:To identify the single nucleotide polymorphisms(SNPs) in the 5' regulatory region of human Toll-like receptor 4(TLR4) gene and to study its effects on the expression of TLR4 protein in Chinese.Methods:The-2242,-1892 and-1837 polymorphic sites in 5' flank region of TLR4 gene identified before were analyzed in Chinese population by using polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP) method.To figure out the function of the SNPs, we further investigated the TLR4 protein levels in 89 whole blood samples with/without lipopolysaccharide(LPS) treatment from healthy person.Results:In the samples of Han population from Chongqing, the minor allele frequencies of-2242,-1892 and-1837 SNPs were 43.27%, 27.70% and 42.75%, separately.Further investigation of the TLR4 protein indicated that the TLR4 expression in leukocytes was higher in heterozyous TC and homozygous CC than in homozygous TT(P0.05) after LPS stimulation in-2242 SNP, while no change was observed in-1892 and-1837 SNPs.Conclusion:Sampling analysis in Han population of Chongqing showed that the-2242 polymorphism of TLR4 may be an important functional variant in Chinese Han population, which might be used as a relevant genetic maker for sepsis in trauma patients.