title: TLR2 and TLR4 polymorphisms in familial Mediterranean fever.
abstract: It has been suggested that MEVF mutations offer advantage against infections, including tuberculosis. Bearing in mind the central role of TLR-2 and TLR-4 in the recognition of pathogens, we conducted this study to examine whether the TLR2-R753Q, TLR4-D299G, TLR4-T399I common polymorphisms are associated with susceptibility to familial Mediterranean fever (FMF) or affect the course of the disease. A cohort of 169 FMF patients and 245 healthy bone marrow donors were enrolled in the study. FMF patients appeared with a significantly lower frequency of the TLR4-D299G mutated allele (3.2% vs 6.9%, p = 0.032). No association was observed with the other analyzed polymorphisms. Moreover, we found no association between polymorphisms and the frequency of attacks or the development of amyloidosis. Our results may reinforce the hypothesis that FMF patients display a better defense against pathogens, providing an additional mechanism and suggesting a positive selection advantage in the area of the Mediterranean basin.
authors.affiliation: Department of Immunology and Histocompatibility, University of Thessaly Medical School, Larissa, Greece. maspel@med.uth.gr
authors.forename: Matthaios
authors.initials: M
authors.lastname: Speletas
authors.forename: Fani
authors.initials: F
authors.lastname: Kalala
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.forename: Vassileios
authors.initials: V
authors.lastname: Papadopoulos
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Merentiti
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000686:Amyloidosis; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium; D011110:Polymorphism, Genetic; D000071198:Pyrin; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4