ARG753GLN POLYMORPHISM OF TOLL-LIKE RECEPTOR 2 GENE IS INCREASED AMONG FMF PATIENTS AND IN THOSE WHO DEVELOP SECONDARY AMYLOIDOSIS

Background: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease that is very common among certain ethnic groups. Secondary amyloidosis is the most serious complication of FMF and is more commonly encountered among patients living in certain areas. Toll-like receptors (TLR) are important molecules of innate immunity. The recognition of environmental pathogens by TLRs results in an inflammatory response, including NF-kappaB activation. The polymorhisms in TLRs may result in an altered course of infectious or inflammatory disease.Objectives: The aim of this study was to investigate whether the Arg753Gln polymorphism of TLR2, which is associated with reduced signaling and change in the intensity of the immune response, had a role in the development of secondary amyloidosis in FMFMethods: The study included 40 patients with secondary amyloidosis due to FMF and 75 FMF patients who had not developed amyloidosis, giving a total of 115 FMF patients. The latter group was on colchicine treatment. The control group consisted of 116 healthy controls.TLR2 gene polymorphism was detected by the PCR-RFLP method.Results: Among 116 healthy controls seven had Arg753Gln polymorphism whereas 29 of the overall 115 patients carried this polymorphism, the difference being significant (p<0.001). This polymorphism was present among 15/40 and 14/75 of the FMF patients with and without amyloidosis, respectively. The difference between these two groups was again significant (p=0.02).Conclusion: This is the first study investigating the association of TLR and the development of secondary amyloidosis in FMF. We have shown that the TLR2 gene Arg753Gln polymorphism was significantly increased among patients with FMF and among the patients who developed secondary amyloidosis. If confirmed in larger studies this genetic variant may offer an explanation for the increased frequency of this complication in geographic areas where infections are more common.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 84Session: Cross talk between genetics, adaptive and innate immunity in childhood auto immune diseases