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. 2009 Dec 10:15:2673-82.

Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan

Yuri Asukata  1 , Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-Ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Hidetoshi Inoko, Shigeaki Ohno, Nobuhisa Mizuki
Affiliations

Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan

Yuri Asukata et al. Mol Vis. .

Abstract

Purpose: 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.

Conclusion: TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.

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Figures

Figure 1
Figure 1
Structure of linkage disequilibrium (LD) plotted for eight SNPs in the TLR4 gene. The D’ value and r2 value (in parentheses) that correspond to each SNP pair are expressed as a percentage and shown within the respective square. The gradient of D’ values (low to high values) is indicated by different shades of red (light to dark, respectively). The eight SNPs constitute a haplotype block that spans 24 kb of TLR4.
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