TY - JOUR
T1 - Functional consequences of toll-like receptor 4 polymorphisms
AU - Ferwerda, Bart
AU - McCall, Matthew B.B.
AU - Verheijen, Karlijn
AU - Kullberg, Bart Jan
AU - Van Der Ven, André J.A.M.
AU - Van Der Meer, Jos W.M.
AU - Netea, Mihai G.
PY - 2008/5
Y1 - 2008/5
N2 - Toll-like receptor 4 (TLR4) is an important pathogen recognition receptor that recognizes mainly lipopolysaccharide (LPS) of Gramnegative bacteria, but also structures from fungal and mycobacterial pathogens, as well as endogenous ligands. Two nonsynonymous polymorphisms of TLR4, Asp299Gly and Thr399Ile, have been suggested to alter the function of the receptor. Some, but not all, studies have proposed that these polymorphisms lead to reduced cytokine response and increased susceptibility to Gram-negative infections. In this review, we compare studies that assessed the effect of the Asp299Gly and Thr399Ile polymorphisms on susceptibility to Gram-negative infections and examine the phenotypic consequences of these polymorphisms. In addition, we review the geographical distribution of TLR4 polymorphisms and present a model for evolutionary pressures on the TLR4 genetic make-up.
AB - Toll-like receptor 4 (TLR4) is an important pathogen recognition receptor that recognizes mainly lipopolysaccharide (LPS) of Gramnegative bacteria, but also structures from fungal and mycobacterial pathogens, as well as endogenous ligands. Two nonsynonymous polymorphisms of TLR4, Asp299Gly and Thr399Ile, have been suggested to alter the function of the receptor. Some, but not all, studies have proposed that these polymorphisms lead to reduced cytokine response and increased susceptibility to Gram-negative infections. In this review, we compare studies that assessed the effect of the Asp299Gly and Thr399Ile polymorphisms on susceptibility to Gram-negative infections and examine the phenotypic consequences of these polymorphisms. In addition, we review the geographical distribution of TLR4 polymorphisms and present a model for evolutionary pressures on the TLR4 genetic make-up.
UR - http://www.scopus.com/inward/record.url?scp=44649115688&partnerID=8YFLogxK
U2 - https://doi.org/10.2119/2007-00135.Ferwerda
DO - https://doi.org/10.2119/2007-00135.Ferwerda
M3 - Review article
C2 - 18231573
SN - 1076-1551
VL - 14
SP - 346
EP - 352
JO - Molecular Medicine
JF - Molecular Medicine
IS - 5-6
ER -