Lai Ning-Sheng, Chou Jian-Liang, Chen Gary C W, Liu Su-Qin, Lu Ming-Chi, Chan Michael W Y
Department of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Dalin, Chia-Yi, Taiwan, ROC.
Mol Biol Rep. 2014 Jun;41(6):3773-80. doi: 10.1007/s11033-014-3242-2. Epub 2014 Feb 16.
In this study, we aim to determine the relationship between methylation level of an inflammatory-related gene, SOCS-1 in serum samples of patients with ankylosing spondylitis (AS) and their degree of inflammation as well as serum cytokine level. Quantitative real time methylation specific PCR was performed to examine the promoter methylation of SOCS-1 in serum samples of 43 HLA-B27+ AS patients and 6 B27+ healthy controls. Degree of inflammation was accessed by spondylopathy, sacroiliitis as well as acute phase reactant, erythrocyte sedimentation rate and C-reactive protein (CRP). Serum IL-6 and TNF-α level was determined by ELISA assay. SOCS-1 methylation can only be found in serums samples from patients but not normal control. Methylation of SOCS-1 significantly associated with severity of patient's spondylopathy (P < 0.005), sacroiliitis (P < 0.005) and acute phase reactant CRP (P = 0.0278). AS patients also exhibited higher serum IL-6 (P < 0.001) and TNF-α level (P < 0.001). Importantly, patients with high serum IL-6 or TNF-α level demonstrated a significantly higher SOCS-1 methylation (P < 0.001). In conclusion, this proof-of-principle study suggested that methylation of SOCS-1 can be detected in serum of HLA-B27+ AS patients but not in B27+ controls. The pathogenic potential of SOCS-1 methylation in AS deserves further investigation.
在本研究中，我们旨在确定强直性脊柱炎（AS）患者血清样本中炎症相关基因SOCS-1的甲基化水平与其炎症程度以及血清细胞因子水平之间的关系。采用定量实时甲基化特异性PCR检测43例HLA-B27阳性AS患者和6例B27阳性健康对照血清样本中SOCS-1的启动子甲基化情况。通过脊柱病、骶髂关节炎以及急性期反应物、红细胞沉降率和C反应蛋白（CRP）来评估炎症程度。采用ELISA法测定血清IL-6和TNF-α水平。仅在患者血清样本中检测到SOCS-1甲基化，正常对照中未检测到。SOCS-1甲基化与患者脊柱病严重程度（P < 0.005）、骶髂关节炎（P < 0.005）及急性期反应物CRP（P = 0.0278）显著相关。AS患者血清IL-6（P < 0.001）和TNF-α水平也较高（P < 0.001）。重要的是，血清IL-6或TNF-α水平高的患者SOCS-1甲基化显著更高（P < 0.001）。总之，这项原理验证研究表明，可在HLA-B27阳性AS患者血清中检测到SOCS-1甲基化，而在B27阳性对照中未检测到。SOCS-1甲基化在AS中的致病潜力值得进一步研究。
