Characterization and functional investigation of single nucleotide polymorphisms (SNPs) in the human TLR5 gene.

Toll-like receptors recognize pathogen-associated molecular patterns (PAMPs) and TLR5 is the pathogen recognition receptor (PRR) for bacterial flagellin. Patients carrying a R392 stop polymorphism display an inflammatory phenotype and increased susceptibility to pneumonia caused by the flagellated bacteria Legionella pneumophila. While this suggests that TLR5 mutations may be clinically relevant, functional data are not available for the majority of the other TLR5 polymorphisms. We have characterized all known single nucleotide polymorphisms (SNPs) of TLR5 for their functional relevance upon stimulation in transiently transfected CHO-K1 cells. Among the 13 missense SNPs of TLR5 reported in the human genetic databases, three SNPs (c.1174C>T, p.R392X; c.2081A>G, p.D694G; and c.2464C>T, p.L822F) were found to be functionally relevant in transiently transfected CHO-K1 cells. The prevalences of these functionally relevant SNPs in our investigation were 11.9 %, 0 %, and 0 %, in healthy donors. The p.D694G and p.L822F SNPs are of low frequency in the Caucasian population though further investigations of the common p.R392X variant alone or of functional relevant TLR5 SNPs in combination with other TLR SNPs will elucidate their possible role on disease susceptibility in humans and may facilitate clinical diagnosis.