The Investigation Of TNFAIP3in Behcet’s Disease, Vogt-koyanagi-harada Syndrome And Fuchs Syndrome

PART1: GENE POLYMORPHISMS CONFER RISK FORBEHCET’S DISEASE, VOGT-KOYANAGI-HARADASYNDROME AND FUCH UVEITIS SYNDROMEPurpose:The tumor necrosis factor alpha inducible protein3(TNFAIP3) genepolymorphisms have recently been reported to be associated with thesusceptibility to several immune-related diseases. This study wasperformed to evaluate the potential association of TNFAIP3polymorphisms with Behcet s disease,Vogt-Koyanagi-Harada syndromeand Fuch Uveitis syndrome in a Chinese Han population.Methods:Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604,rs7753873, rs5029928and rs9494885of TNFAIP3were genotyped in722BD patients,834VKH syndrome patients,225Fuchs syndrome patientsand1415healthy controls using a PCR-restriction fragment length polymorphism assay.Results:1. The results showed that the five SNPs rs10499194, rs610604,rs7753873,rs5029928and rs9494885of TNFAIP3were in Hardy-Weinbergequilibrium in the cases and controls (p>0.05).2. The results showed that there were significant differences betweenBD patients and controls concerning the frequencies of rs9494885,rs10499194, and rs7753873. The significantly increased frequencies of thers9494885TC genotype and C allele were found in BD patients comparedwith controls (pc=1.839×10-10, OR2.02,95%CI1.65–2.49; pc=8.359×10-10, OR1.81,95%CI1.51–2.18, respectively). The frequencies of theTT genotype and T allele were significantly lower in BD patients than thatin controls (pc=1.239×10-10, OR0.50,95%CI0.40–0.61; pc=8.359×10-10,OR0.55,95%CI0.46–0.66,respectively). The frequencies of the rs10499194CCgenotype (pc=0.015,OR1.96,95%CI1.30–2.97) and C allele (pc=0.005,OR1.924,95%CI1.28–2.90) were higher in BD patients than that incontrols. The frequencies of the rs10499194TC genotype (pc=0.015, OR0.51,95%CI0.34–0.77) and T allele (pc=0.005,OR0.52,95%CI0.35–0.78)were lower in BD patients than that in controls. For rs7753873, the higherfrequencies of the AC genotype (pc=0.015, OR1.49,95%CI1.17–1.91)and C allele (pc=0.025,OR1.39,95%CI1.11–1.76),and the lowerfrequencies of the AA genotype (pc=0.03, OR0.68,95%CI0.53–0.87) and A allele (pc=0.025, OR0.72,95%CI0.57–0.91) were found in BDpatients compared with controls. There was no association of BD withrs610604or with rs5029928.3.The results showed the signifcantly increased frequencies of thers9494885TC genotype and C allele in VKH disease patients comparedwith that in controls (corrected p (pc)=2.264×105, OR1.640; pc=1.093×105, OR1.551, respectively). The frequencies of the TT genotypeand T allele of rs9494885were markedly lower in VKH disease patients ascompared with that in controls (p5c=1.118×10, OR=0.605; pc=1.093×105,OR=0.645, respectively). No association was found between rs10499194,rs610604, rs7753873and rs5029928polymorphisms withVKH disease.4.The genotypic and allelic frequencies of rs10499194, rs610604,rs7753873, rs5029928and rs9494885of TNFAIP3were not differentbetween patients with Fuchs syndrome and controls.Conclusions:1. This study identified a novel association between SNP rs9494885inTNFAIP3and BD in a Chinese Han population. The results suggest that thers9494885TT genotype and T allele of TNFAIP3could provide strongprotection against BD. The rs9494885TC genotype and C allele werehigh-risk factors for this disease. Our study also showed that SNPsrs10499194and rs7753873were weakly associated with susceptibility toBD. The CC genotype and C allele of rs10499194, and the AC genotype and C allele of rs7753873were the risk factors for BD whereby the AAgenotype and A allele of rs7753873, and the TC genotype and T allele ofrs10499194provided protection.2. To our knowledge this is the first report describing the associationof TNFAIP3gene polymorphism with VKH disease in a Chinese Hanpopulation. The results suggest that the rs9494885TC genotype and Callele may be predisposing factors to VKH disease, whereas the rs9494885TT genotype and T allele may provide protection against this disease.3. Our results suggest five sites of TNFAIP3are not associated withFuchs syndrome in the Chinese Han population. PART2: EFFECTS OF RS9494885TWO GENOTYPES ON THEEXPRESSION OF TNFAIP3IN PBMCS FROM HEALTHYINDIVIDUALSPurpose:Examine TNFAIP3expression with two genotypes of SNP rs9494885in PBMCs from healthy individuals.Methods:Real-time PCR analysis of TNFAIP3expression in PBMCs derivedfrom healthy individuals of SNP rs9494885TT, and TC genotypes.Results:The results showed that there was no difference in TNFAIP3expression between individuals with the TT or TC genotype.Conclusions:This study suggests that the diseases associated SNP rs9494885maybe involved in this disease through an unknown mechanisms rather thandirectly regulating TNFAIP3transcriptional regulation. Other mechanismsmay need further research.