title: Arg753Gln TLR-2 polymorphism in familial mediterranean fever: linking the environment to the phenotype in a monogenic inflammatory disease.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) is an autoinflammatory disease common in eastern Mediterranean populations. The most severe complication is the development of secondary amyloidosis. Toll-like receptor (TLR-2) plays a critical role in linking the recognition of microbes to immune activation. We investigated whether the Arg753Gln TLR2 polymorphism affected the development of secondary amyloidosis in patients with FMF.
  
  
  METHODS
  We studied 75 patients with FMF, 40 patients with FMF who developed secondary amyloidosis, and 116 healthy controls. TLR2 gene Arg753Gln mutations were analyzed with a polymerase chain reaction-restriction fragment length polymorphism method.
  
  
  RESULTS
  The frequency of the Arg753Gln TLR2 polymorphism among the Turkish population was 6%, whereas it was 25.2% among patients with FMF (p < 0.01). The difference of the frequency of the polymorphism between FMF patients with and without amyloidosis was significant: 15/40 (37.5%) and 14/75 (18.6%), respectively (p = 0.02).
  
  
  CONCLUSIONS
  The Arg753Gln polymorphism may affect the severity of this monogenic disease by influencing the innate immune response to pathogens. The presence of the polymorphism may influence the phenotype of FMF in geographic areas where bacterial insult is more common.
authors.affiliation: Department of Pediatrics, Hacettepe University, Ankara, Turkey. sezaozen@hacettepe.edu.tr
authors.forename: Seza
authors.initials: S
authors.lastname: Ozen
authors.forename: Afig
authors.initials: A
authors.lastname: Berdeli
authors.forename: Banu
authors.initials: B
authors.lastname: Türel
authors.forename: Sim
authors.initials: S
authors.lastname: Kutlay
authors.forename: Fatos
authors.initials: F
authors.lastname: Yalcinkaya
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arici
authors.forename: Nesrin
authors.initials: N
authors.lastname: Besbas
authors.forename: Aysin
authors.initials: A
authors.lastname: Bakkaloglu
authors.forename: Engin
authors.initials: E
authors.lastname: Yilmaz
mesh_terms: D000686:Amyloidosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000235:genetics; D004777:Environment; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D005973:Glutamine; D001120:Arginine