研究 TXNDC5 在类风湿关节炎中的致病作用。
Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis.
机构信息
National Laboratory for Bio-Drugs of Ministry of Health, Provincial Laboratory for Modern Medicine and Technology of Shandong, Research Center for Medicinal Biotechnology, Shandong Academy of Medical Sciences, Jingshi Road 18877, Jinan, Shandong, 250062, PR China.
出版信息
Arthritis Res Ther. 2011 Jul 29;13(4):R124. doi: 10.1186/ar3429.
INTRODUCTION
Expression of TXNDC5, which is induced by hypoxia, stimulates cell proliferation and angiogenesis. Our previous study detected increased TXNDC5 expression in the synovial tissues of rheumatoid arthritis (RA) patients using proteomic methods. The current study investigated a pathogenic role for TXNDC5 in RA.
METHOD
Expression of TXNDC5 in synovial membranes was quantitatively analyzed by immunohistochemistry, Western blotting and real-time polymerase chain reaction (PCR). Serum TXNDC5 levels and serum anti-TXNDC5 antibody levels were determined using sandwich enzyme-linked immunosorbent assay (ELISA). A total of 96 single nucleotide polymorphisms (SNPs) in or near the TXNDC5 gene were genotyped using custom-designed Illumina 96-SNP VeraCode microassay. Allele frequencies and genotype frequencies of SNPs were assessed using a case-control design in a cohort of 267 Chinese patients with RA, 51 patients with ankylosing spondylitis (AS) and 160 healthy controls. Additional genotyping of 951 patients with RA and 898 healthy controls was performed for four SNPs (rs2277105, rs369086, rs443861 and rs11962800) using the TaqMan method.
RESULTS
Real-time PCR, Western blotting and immunohistochemistry detected significantly higher TXNDC5 expression in the synovial tissues of RA patients compared to samples from patients with osteoarthritis (OA) or AS. ELISA detected significantly higher levels of TXNDC5 in the blood of RA patients compared to OA, AS and systemic lupus erythematosus patients, and healthy controls. ELISA did not detect significantly different levels of anti-TXNDC5 antibody in the blood of RA, OA and AS patients and healthy controls. A total of 9 SNPs (rs9505298, rs41302895, rs1225936, rs1225938, rs372578, rs443861, rs408014, rs9392189 and rs2743992) showed significant association with RA, while 16 SNPs (rs1044104, rs1225937, rs1225938, rs372578, rs89715, rs378963, rs1225944, rs1225947, rs1238994, rs369086, rs408014, rs368074, rs1225954, rs1225955, rs13209404 and rs3812162) showed significant association with AS. Taqman SNP assay demonstrated that rs443861 has an association with RA, which correlates with the microassay results.
CONCLUSIONS
TXNDC5 is up-regulated in synovial tissues of RA patients. TXNDC5 has a genetic effect on the risk of RA and AS.
简介
TXNDC5 的表达受缺氧诱导，刺激细胞增殖和血管生成。我们之前的研究使用蛋白质组学方法检测到类风湿关节炎 (RA) 患者的滑膜组织中 TXNDC5 表达增加。本研究探讨了 TXNDC5 在 RA 中的致病作用。
方法
通过免疫组织化学、Western blot 和实时聚合酶链反应 (PCR) 定量分析滑膜膜中 TXNDC5 的表达。使用夹心酶联免疫吸附测定法 (ELISA) 测定血清 TXNDC5 水平和血清抗 TXNDC5 抗体水平。使用定制设计的 Illumina 96-SNP VeraCode 微阵列对 TXNDC5 基因内或附近的 96 个单核苷酸多态性 (SNP) 进行基因分型。使用病例对照设计在 267 例中国 RA 患者、51 例强直性脊柱炎 (AS) 患者和 160 例健康对照者中评估 SNP 的等位基因频率和基因型频率。使用 TaqMan 方法对 951 例 RA 患者和 898 例健康对照者的四个 SNP(rs2277105、rs369086、rs443861 和 rs11962800)进行了 951 例 RA 患者和 898 例健康对照者的额外基因分型。
结果
实时 PCR、Western blot 和免疫组织化学检测到 RA 患者滑膜组织中 TXNDC5 表达明显高于骨关节炎 (OA) 或 AS 患者。ELISA 检测到 RA 患者血液中的 TXNDC5 水平明显高于 OA、AS 和系统性红斑狼疮患者，以及健康对照者。ELISA 未检测到 RA、OA 和 AS 患者及健康对照者血液中抗 TXNDC5 抗体水平有显著差异。9 个 SNP(rs9505298、rs41302895、rs1225936、rs1225938、rs372578、rs443861、rs408014、rs9392189 和 rs2743992)与 RA 显著相关，而 16 个 SNP(rs1044104、rs1225937、rs1225938、rs372578、rs89715、rs378963、rs1225944、rs1225947、rs1238994、rs369086、rs408014、rs368074、rs1225954、rs1225955、rs13209404 和 rs3812162)与 AS 显著相关。Taqman SNP 检测显示 rs443861 与 RA 相关，与微阵列结果一致。
结论
TXNDC5 在 RA 患者的滑膜组织中上调。TXNDC5 对 RA 和 AS 的发病风险有遗传影响。
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