The Association Between Fc Receptor Family Genetic Polymorphisms With Behcet's Disease And Vogt-Koyanagi-Harada Syndrome

Background:Fc receptors are known to have a pivotal role in the initiation and regulation of many immunological and inflammatory processes,and gene polymorphisms identified so far,contribute to the development of a range of chronic inflammatory and autoimmune diseases.Uveitis is a common and important eye disease which can cause apermanentloss of vision.Beh?et's disease(BD)and Vogt–Koyanagi–Harada(VKH)syndrome,manifestingasabilateral panuveitis,are two of the most common uveitis entities primarily prevalent in China.The association between Fc receptor family genetic polymorphisms with BD and VKH has however not yet been tested in a large cohort of Chinese Han patients.Purposes:This study aimed to investigate the association of Fc receptor family gene polymorphisms with ocular BD and VKH syndrome in Han Chinese.Methods:A two stage case–control study was performed in 1022 BD cases,467 VKH cases and 1803 healthy controls.Twenty-three single nucleotide polymorphisms(SNPs)were genotyped using the MassARRAY system(Sequenom),TaqMan SNP Genotyping Assay and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method.Differences of genotype and allele frequencies between cases and controls were analyzed using the?2 test with the SPSS 17.0 software.The expression of FCGR3A was examined by real-time PCR and cytokine production was measured by enzyme linked immunosorbent assay(ELISA).FCGR3A expression levels and various cytokines between the two genotype groups were analyzed by the independent samples T-test or nonparametric Mann-Whitney U test.Result:In the first-stage study of BD,a decreased frequency of the FCGR3A/rs428888 CC genotype was found in cases(Pc=2.02×10^–2,OR=0.551).The frequency of the FCGR3A/rs428888 CT genotype in BD was significantly higher compared to controls(Pc=2.02×10^–2,OR=1.814)(Table 2).No statistically significant association was found between the other 22 SNPs tested and ocular BD.the second phase and combined study confirmed the association of FCGR3A/rs428888 with BD.The combined data showed a stronger significant association of rs428888 in FCGR3A with BD and a lower frequencies of CC genotype and C allele.(CC genotype:Pc=1.96×10^-7,OR=0.527;C allele:Pc=7.22×10^-7,OR=0.554;CT genotype:Pc=1.96×10^-7;OR=1.897 respectively).Functional experiments showed an increased FCGR3A expression(P=0.005)and increased cytokine protein expressions of MCP-1,IL-1?and TNF-?by LPS stimulated PBMCs in CT carriers of FCGR3A rs428888 compared to CC carriers(P=0.034;P=0.025;P=0.04;respectively).No association betweenthegenepolymorphismsdescribedaboveandVKH syndrome could be detected.Conclusions:Our findings demonstrate that FCGR3A/rs428888confers genetic susceptibility for BD in Han Chinese by modulating the expression of FCG3A.