| Background:P2X7 is Purinergic receptor P2X, ligand-gated ion channel 7. The P2RX7 gene (coding for P2X7 purinergic receptor) is a susceptibility gene in inflammatory and immune diseases. P2X7 can integrate downstream phosphatidylinositol-3 kinase/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/mTOR/p70S6K) pathway. Enrichment Analysis Approach of our Genome-wide association (GWAS) study with Vogt-Koyanagi-Harada syndrome (VKH) showed that single nucleotide polymorphisms (SNPs) were rich in the PI3K/mTOR/p70S6K axis, which was proved important for lymphocyte development and differentiation. The pathogenesis of uveitis is associated with immune related factors. We initial this study presuming loci in P2RX7-PI3K/mTOR/p70S6K axis may be susceptible for uveitis.Objective:The objective of our study was to investigate the genetic susceptibility of P2X7-PI3K/mTOR/p70S6K pathway with VKH syndrome and Behcet’s disease in Han Chinese population.Methods:A two stage case-control study was performed.404 patients with Behcet’s disease,380 patients with VKH syndrome and 595 controls were recruited for the screening stage,420 patients with Behcet’s diseaseand 448 controls for the replication stage. We use polymerase chain restriction fragment length polymorphism (PCR-RFLP) methodology and TaqMan SNP Genotyping Assay for genotyping. Frequencies of genotypes and alleles were counted by direct counting and compared by Chi-squaretesting (X2 test)Results:The frequencies of CC, CT genotype and C allele of rs1718119 in P2RX7 were different in Behcet’s disease (Pc=0.02, OR=1.786;Pc=0.039, OR=0.569;Pc=0.02,OR=1.685). The replication and combining studies confirm the association (Replication:CC Pc=0.01, OR=1.809; CT Pc=0.03, OR=0.576; C Pc=0.01, OR=1.740; Combination: CC Pc=2.99×10-5, OR=1.798; CT Pc=1.77×10-4, OR=0.573; C Pc=2.98×10-5, OR=1.714). The other nine SNPs in Behcet’s diseas and all ten candidate SNPs in VKH syndrome were found no significant differences (P>0.05).Conclusion:Our study revealed an association of rs1718119 in P2RX7 with Behcet’s diseas in Han Chinese population. |
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