Lijun Zhang1, Hongsong Yu1, Minming Zheng1, Hua Li1, Yunjia Liu1, Aize Kijlstra2, Peizeng Yang1. 1. The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China. 2. University Eye Clinic Maastricht, Maastricht, The Netherlands.
Abstract
PURPOSE: Behçet's disease (BD) is a common uveitis entity in China. The endoplasmic reticulum aminopeptidase 1 (ERAP1), has a significant influence on the stability and immunological properties of MHC-I loaded peptides. In the present study, we investigated the association of ERAP1 gene polymorphisms with BD in a Chinese Han population. METHODS: A two-stage case-control study was carried out in 930 BD patients and 1704 healthy controls. 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 TaqMan SNP genotyping assay. Furthermore, ERAP1 expression in peripheral blood mononuclear cells (PBMCs) was examined in genotyped individuals by real-time PCR. RESULTS: The result demonstrated that the frequencies of the A allele of rs1065407 and C allele of rs10050860 were significantly decreased in BD patients (Pc = 8.5 × 10-8, OR = 0.51; Pc = 1.1 × 10-5, OR = 0.54, respectively). No significant association was observed for the other six 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 = 3.8 × 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.
PURPOSE: Behçet's disease (BD) is a common uveitis entity in China. The endoplasmic reticulum aminopeptidase 1 (ERAP1), has a significant influence on the stability and immunological properties of MHC-I loaded peptides. In the present study, we investigated the association of ERAP1 gene polymorphisms with BD in a Chinese Han population. METHODS: A two-stage case-control study was carried out in 930 BDpatients and 1704 healthy controls. 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 TaqMan SNP genotyping assay. Furthermore, ERAP1 expression in peripheral blood mononuclear cells (PBMCs) was examined in genotyped individuals by real-time PCR. RESULTS: The result demonstrated that the frequencies of the A allele of rs1065407 and C allele of rs10050860 were significantly decreased in BDpatients (Pc = 8.5 × 10-8, OR = 0.51; Pc = 1.1 × 10-5, OR = 0.54, respectively). No significant association was observed for the other six 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 BDpatients not receiving immunosuppression was significantly lower than that in healthy controls (P = 3.8 × 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.
Authors: Masaki Takeuchi; Michael J Ombrello; Yohei Kirino; Burak Erer; Ilknur Tugal-Tutkun; Emire Seyahi; Yilmaz Özyazgan; Norman R Watts; Ahmet Gül; Daniel L Kastner; Elaine F Remmers Journal: Ann Rheum Dis Date: 2016-05-23 Impact factor: 19.103