Putative association of a TLR9 promoter polymorphism with atopic eczema.
BACKGROUND
Toll-like receptors (TLR) play a pivotal role in the induction of first-line defense mechanisms of the innate immune system and trigger adaptive immune responses to microbial pathogens. Genetic variations in innate immunity genes have been reported to be associated with a range of inflammatory disorders. Deficiencies on the level of immunity receptors such as pathogen-recognition receptors are suspected to affect the maturation of our immune system and to avail thereby the high prevalence of atopic diseases and susceptibility of atopic patients to microbial infections.


OBJECTIVE
We evaluated TLR9 as susceptibility gene for atopic eczema (AE).


METHODS
Analyses of four tag single-nucleotide polymorphisms in two panels of families containing a total of 483 parent-affected offspring trios as well as a cohort of 274 unrelated adult AE cases and 252 hypernormal population-based controls have been performed.


RESULTS
In both family cohorts, polymorphism C-1237T, which is located within the promoter region of the TLR9 gene, was significantly associated with AE, in particular the intrinsic subtype of AE. No associations were seen in the case-control cohort. Luciferase reporter gene assays revealed significantly higher promoter activity of the TT allelic variant at this single nucleotide polymorphism site.


CONCLUSIONS
These observations suggest that the TLR9 promoter polymorphism C-1237T might affect AE susceptibility in particular in patients with the intrinsic variant of AE.
Novak
N
N
Department of Dermatology, University of Bonn, Bonn, Germany.
Yu
C-F
CF
Bussmann
C
C
Maintz
L
L
Peng
W-M
WM
Hart
J
J
Hagemann
T
T
Diaz-Lacava
A
A
Baurecht
H-J
HJ
Klopp
N
N
Wagenpfeil
S
S
Behrendt
H
H
Bieber
T
T
Ring
J
J
Illig
T
T
Weidinger
S
S
D000328:Adult; D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9