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Tissue Antigens
Article . 2011 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
Tissue Antigens
Article . 2012
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Genetic variation in the Toll‐like receptor gene cluster (TLR10‐TLR1‐TLR6) influences disease course in sarcoidosis

Authors: Henk J.T. Ruven; Ger T. Rijkers; Marcel Veltkamp; C.H.M. van Moorsel; Jan C. Grutters;

Genetic variation in the Toll‐like receptor gene cluster (TLR10‐TLR1‐TLR6) influences disease course in sarcoidosis

Abstract

Sarcoidosis is an inflammatory disease of unknown etiology. Various microorganisms have been proposed as etiologic agent suggesting a role for pattern‐recognition receptors such as Toll‐like receptors (TLRs) in disease pathogenesis, with a special interest in TLR‐2. TLR‐10, TLR‐1, and TLR‐6 act as co‐receptors for TLR‐2 and the genes encoding these receptors are located in a gene cluster on chromosome 4. The aim of our study was to assess differences in genetic variation in the TLR10‐TLR1‐TLR6 gene cluster between patients and controls. A total of eight single nucleotide polymorphisms were genotyped in 447 healthy controls and 533 patients, divided in 425 with sarcoidosis and 108 with Löfgren's syndrome. Comparison of the total patient cohort with controls showed that the allele frequencies of rs1109695, rs7658893 (TLR‐10), and rs5743604 as well as rs5743594 (TLR‐1) differed significantly. Haplotype analysis showed that the most common haplotype found was significantly decreased in patients with chronic sarcoidosis. Furthermore, a less common haplotype was found to be significantly increased in patients with Löfgren's syndrome as well as sarcoidosis patients with self‐remitting disease, indicating that it could act as a disease modifying haplotype. In conclusion, our study suggests that absence of the common haplotype in the TLR10‐TLR1‐TLR6 gene cluster increases the risk of developing chronic disease in patients already affected by sarcoidosis. Based on their role as co‐receptors for TLR‐2, this study supports the growing evidence that aberrant TLR‐2 function is important in sarcoidosis disease pathogenesis.

Related Organizations
Keywords

Male, Sarcoidosis, Polymorphism, Single Nucleotide, Toll-Like Receptor 1, Toll-Like Receptor 2, Cohort Studies, Toll-Like Receptor 6, Gene Frequency, Haplotypes, Multigene Family, Toll-Like Receptor 10, Chronic Disease, Humans, Female, Alleles

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
61
Top 10%
Top 10%
Top 10%