Arg753Gln TLR-2 polymorphism in familial mediterranean fever: linking the environment to the phenotype in a monogenic inflammatory disease.
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.
Ozen
Seza
S
Department of Pediatrics, Hacettepe University, Ankara, Turkey. sezaozen@hacettepe.edu.tr
Berdeli
Afig
A
Türel
Banu
B
Kutlay
Sim
S
Yalcinkaya
Fatos
F
Arici
Mustafa
M
Besbas
Nesrin
N
Bakkaloglu
Aysin
A
Yilmaz
Engin
E
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
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D005973:Glutamine; D001120:Arginine