Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.
Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.
Faber
Joerg
J
Children's Hospital, Johannes Gutenberg-University, Mainz, Germany. faber@uni-mainz.de
Meyer
Claudius U
CU
Gemmer
Christina
C
Russo
Alexandra
A
Finn
Adam
A
Murdoch
Craig
C
Zenz
Werner
W
Mannhalter
Christine
C
Zabel
Bernhard U
BU
Schmitt
Heinz-J
HJ
Habermehl
Pirmin
P
Zepp
Fred
F
Knuf
Markus
M
D000367:Age Factors; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000235:genetics* / Q000276:immunology*; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004247:DNA