title: 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.
abstract: 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-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms seem to affect the development of secondary amyloidosis in FMF patients in our study population.
authors: Department of Pediatrics, Dokuz Eylül University Medical Faculty, İzmir, Turkey. alper.soylu@deu.edu.tr
authors: Alper
authors: A
authors: Soylu
authors: Halil
authors: H
authors: Ateş
authors: Sultan
authors: S
authors: Cingöz
authors: Mehmet
authors: M
authors: Türkmen
authors: Belde Kasap
authors: BK
authors: Demir
authors: Mehmet
authors: M
authors: Tunca
authors: Meral
authors: M
authors: Sakızlı
authors: Mustafa
authors: M
authors: Cirit
authors: Rıfkı
authors: R
authors: Ersoy
authors: Ayfer
authors: A
authors: Ulgenalp
authors: Salih
authors: S
authors: Kavukçu
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000686:Amyloidosis / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D011110:Polymorphism, Genetic; D000685:Serum Amyloid A Protein / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D000685:Serum Amyloid A Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4