Affiliations: University Children's Hospital, University of
Freiburg, Mathildenstrasse 1, D-79106 Freiburg, Germany | St. Josef's Hospital, Sautier Str. 1, D-79104
Freiburg, Germany
Note: [] Corresponding author: Dr. Andrea Heinzmann, University
Children's Hospital, University of Freiburg, Mathildenstr. 1, D-79106 Freiburg,
Germany. Tel.: +49 761 2706371; Fax: +49 761 2706372; E-mail:
[email protected]
Abstract: 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⩽ 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.
Keywords: Association, CD14, genetics, RSV, TLR4
Journal: Disease Markers, vol. 22, no. 5-6, pp. 303-308, 2006
