| Background: Beh?et’s disease is a common uveitis entity in China. It is one of the multisystem autoimmune or autoinflammatory diseases characterized by recurrent ulcerations of the oral cavity and genitalia, representative skin lesions and severe ocular inflammation. The human leukocyte antigen（HLA）-B51 has been proven as the strongest risk gene for Beh?et’s disease. Recent studies have indicated that Endoplasmic reticulum amino peptidase1（ERAP1） has a significant influence on the stability and immunological properties of MHC-I loaded peptides. Polymorphisms of the ERAP1 gene have shown to be associated with various autoimmune diseases susceptibility. The association of genetic variants of ERAP1 with the susceptibility of Beh?et’s disease in a Chinese Han population has however not yet been reported and was therefore the subject of the study presented here.Purposes:To investigated the association of ERAP1 gene polymorphisms with Beh?et’s disease in a Chinese Han population.Methods: Seven single nucleotide polymorphisms（SNPs） of the ERAP1 gene were determined using a PCR restriction fragment length polymorphism（PCR-RFLP） assay and one SNP was genotyped by Taq Man? SNP genotyping assay in 930 Beh?et’s disease patients and 1704 healthy controls. Genotype distributions and allele frequencies were compared using χ2 analysis between Beh?et’s disease patients and normal controls. Stratified analysis was also performed according to sex. Furthermore, ERAP1 expression in peripheral blood mononuclear cells（PBMCs） was examined in genotyped individuals by Real-time PCR.RESULTS: The frequencies of the A allele and AA genotype of ERAP1-rs1065407 were significantly decreased in BD patients(Pc=3.226×10-8, OR=0.51; Pc=2.714×10-7, OR=0.50, respectively). The frequency of the ERAP1-rs1065407 AC genotype was significantly increased in BD patients compared with healthy controls(Pc=2.429×10-6, OR=1.92). Decreased frequencies of the ERAP1-rs10050860 C allele and CC genotype were observed in BD patients as compared with normal controls(Pc=3.529×10-6, OR=0.54; Pc=3.086×10-5, OR=0.54, respectively). A stratified analysis of the main associations by gender showed that the genotype and allele frequencies for ERAP1-rs1065407 showed significant differences between patients and controls in both male and female patients. However, the genotype and allele frequencies for ERAP1-rs10050860 showed more significant differences in male compared to that in female patients. No significant association was observed for the other 6 SNPs. ERAP1 expression in AA carriers of rs1065407 and CC carriers of rs10050860 was higher than that observed in AC/CC carriers（P=0.022） or CT/TT carriers（P=0.018） by LPS stimulated PBMCs, respectively. In addition, the expression of ERAP1 in active BD patients not receiving immunosuppression was significantly lower than that in healthy controls(P=3.762×10-4).Conclusions: Our study showed that rs1065407 and rs10050860 of the ERAP1 gene may contribute to the genetic susceptibility of BD by modulating the expression of ERAP1. |
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