Association of ERAP1 Gene Polymorphisms With Behcet's Disease in Han Chinese
Association of ERAP1 Gene Polymorphisms With Behcet's Disease in Han Chinese
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DOI：
10.1167/iovs.15-17544
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发表时间：
2015-09-01
影响因子：
4.4
通讯作者：
Yang, Peizeng
中科院分区：
文献类型：
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作者：
Zhang, Lijun;Yu, Hongsong;Yang, Peizeng
目的.白塞病是我国常见的葡萄膜炎。内质网氨肽酶1（ERAP 1）对MHC-I负载肽的稳定性和免疫学性质具有显著影响。在本研究中，我们调查了ERAP 1基因多态性与BD在中国汉族人群。对930例BD患者和1704例健康对照者进行了两阶段病例对照研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测ERAP 1基因的7个单核苷酸多态性（SNP），并采用TaqMan SNP基因分型方法对1个SNP进行基因分型。此外，ERAP 1在外周血单核细胞（PBMC）的表达进行了检查基因分型的个人通过实时PCR。结果显示，BD患者rs 1065407的A等位基因和rs 10050860的C等位基因频率显著降低（Pc = 8.5 × 10 ~（-8），OR = 0.51; Pc = 1.1 × 10 ~（-5），OR = 0.54）。其他6个SNPs没有观察到显著关联。rs 1065407的AA携带者和rs 10050860的CC携带者的ERAP 1表达分别高于AC/CC携带者（P = 0.022）和CT/TT携带者（P = 0.018）。此外，ERAP 1在未接受免疫抑制的活动期BD患者中的表达显著低于健康对照组（P = 3.8 × 10 - 4）。我们的研究表明ERAP 1基因的rs 1065407和rs 10050860可能通过调节ERAP 1的表达而参与BD的遗传易感性。
PURPOSE. Behcet'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 x 10(-8), OR = 0.51; Pc = 1.1 x 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 x 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.