Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan.
OBJECTIVE
Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population.


METHODS
Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects.


RESULTS
We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'>/=0.78), which were located in one haplotype block.


CONCLUSIONS
TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.
Asukata
Yuri
Y
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Ota
Masao
M
Meguro
Akira
A
Katsuyama
Yoshihiko
Y
Ishihara
Mami
M
Namba
Kenichi
K
Kitaichi
Nobuyoshi
N
Morimoto
Shin-Ichiro
S
Kaburaki
Toshikatsu
T
Ando
Yasutaka
Y
Takenaka
Shinobu
S
Inoko
Hidetoshi
H
Ohno
Shigeaki
S
Mizuki
Nobuhisa
N
D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012507:Sarcoidosis / Q000150:complications* / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014605:Uveitis / Q000150:complications* / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4