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TLR Polymorphisms in FMF: Association of TLR-2 (Arg753Gln) and TLR-4 (Asp299Gly, Thre399Ile) Polymorphisms and Myeloid Cell TLR-2 and TLR-4 Expression with the Development of Secondary Amyloidosis in FMF.
MedLine Citation:
PMID:  20714796     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Amyloidosis is the major complication of familial Mediterranean fever (FMF). Toll-like receptors (TLR) are involved in the activation of an innate immune system TLR-2 and TLR-4 recognize lipoteichoic acid and lipopolysaccharides (LPS), respectively. While TLR-2 Arg753Gln polymorphism upregulates, TLR-4 Asp299Gly and Thre399Ile polymorphisms downregulate inflammation. We investigated the effect of these polymorphisms on the development of amyloidosis in FMF patients. We also investigated myeloid cell TLR-2 and TLR-4 expressions in these patients. We studied 26 FMF patients and 13 FMF patients with amyloidosis. TLR-2 Arg753Gln and TLR-4 Asp299Gly and Thr399Ile polymorphisms were analyzed with the polymerase chain reaction-restriction fragment length polymorphism method. Myeloid cell baseline TLR-2 and TLR-4 and LPS-induced TLR-4 expressions were evaluated. The TLR-2 and TLR-4 polymorphism rate was compared with the results of 100 healthy subjects in our previous study. In addition, 13 healthy controls were enrolled for leukocyte TLR-2 and TLR-4 expressions. Serum amyloid A (SAA) levels were measured in these 13 control cases and in FMF patients during attack-free periods. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls in our previous study were 1%, 3%, and 2%, respectively. The frequency of these polymorphisms were not different in FMF patients (with or without amyloidosis) compared to the control group. Likewise, myeloid cell TLR-2 and TLR-4 expressions were not different among the controls and FMF patients. However, LPS-induced TLR-4 expression in granulocytes was more prominent in FMF patients. There was no correlation between TLR-2 and TLR-4 expressions and SAA levels. Neither myeloid cell TLR-2 and TLR-4 expressions nor TLR-3 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms seem to affect the development of secondary amyloidosis in FMF patients in our study population.
Authors:
Alper Soylu; Halil Ateş; Sultan Cingöz; Mehmet Türkmen; Belde Kasap Demir; Mehmet Tunca; Meral Sakızlı; Mustafa Cirit; Rıfkı Ersoy; Ayfer Ulgenalp; Salih Kavukçu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inflammation     Volume:  34     ISSN:  1573-2576     ISO Abbreviation:  Inflammation     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  379-87     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Dokuz Eylül University Medical Faculty, İzmir, Turkey, alper.soylu@deu.edu.tr.
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