Abstract
The present study was designed to explore the interrelationship between single nucleotide polymorphisms (SNP) of the tumor necrosis factor superfamily (TNFSF) and its respective receptor superfamily (TNFRSF) genes and Behcet's disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) in Han Chinese. The study sample included 796 patients with BD, 792 patients with VKH syndrome, and 1604 healthy controls. The genotyping of 35 SNPs was performed by MassARRAY platform (Sequenom), iPLEX Gold Assay, PCR-restriction fragment length polymorphism assay and TaqMan SNP assay. The mRNA expression levels of TNFSF4, TNFSF8 and TNFSF15 were analyzed by real-time PCR. The IL-6 and TNF-α expression levels were measured by ELISA. The A allele and AA genotype frequencies of TNFSF4/rs1234313 were significantly increased, and the GG genotype frequency of rs1234313 was decreased in subjects with BD. Significantly lower frequencies of the C allele and the CC genotype and higher frequencies of the TT and CT genotypes of TNFSF15/rs4246905 were observed in BD patients. A decreased frequency of the A allele of TNFSF8/rs7028891 was observed in BD patients. The expression of TNFSF15 in CT carriers was significantly higher than that in CC/TT individuals. Increased IL-6 expression and TNF-α production were found in the TNFSF15 CT carriers compared with the CC/TT genotype carriers. No significant differences were observed between the VKH patients and controls. This study indicates that TNFSF4, TNFSF15 and TNFSF8 may participate in the susceptibility to BD among Han Chinese.