TLR-4 and CD14 polymorphisms in respiratory syncytial virus associated disease.
Respiratory syncytial virus (RSV) is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4)/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14. We genotyped the CD14 promotor polymorphism -C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test, haplotypes were calculated by FAMHAP, FASTEHPLUS and Arlequin. All polymorphisms were in Hardy Weinberg Equilibrium. We found marginal association between amino acid exchange D259G in TLR4 with RSV infection p=0.0545). Furthermore, haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe RSV infection (p<or= 0.0010). In contrast, the promotor polymorphism within CD14 was not associated with susceptibility to RSV disease. We conclude from our study, that TLR4 polymorphisms, and particularly the haplotypes, may influence the genetic predisposition to severe RSV infection.
Puthothu
Beena
B
University Children's Hospital, University of Freiburg, Mathildenstrasse 1, D-79106 Freiburg, Germany.
Forster
Johannes
J
Heinzmann
Andrea
A
Krueger
Marcus
M
D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics*; D012136:Respiratory Syncytial Viruses; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4