Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
Biochem Genet. 2024 Dec;62(6):4603-4618. doi: 10.1007/s10528-024-10675-y. Epub 2024 Feb 12.
In recent years, the impact of methylation modifications on Dickkopf-1 (DKK1) in relation to ankylosing spondylitis (AS) has remained elusive. Our objective was to investigate the potential link between DKK1 methylation patterns and transcript levels and AS susceptibility. DNA methylation level of DKK1 was measured in 82 AS and 82 healthy controls (HCs) using targeted bisulfite sequencing. In addition, the transcript level of DKK1 in peripheral blood mononuclear cells from 35 AS patients and 35 HCs was detected using real-time quantitative transcription-polymerase chain reaction. Our study showed that the DKK1 was significantly hypomethylated in AS patients (P < 0.001). The Receiver operating characteristic curve (ROC) showed that DKK1 methylation may be a potential biomarker. The results showed that the difference in DKK1 transcript levels between AS and HCs was not statistically significant. Further analysis showed that DKK1 methylation levels were positively correlated with age and negatively correlated with C-reactive protein levels, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). The methylation level of DKK1 in PBMC of AS patients was significantly lower than that of HCs, and DKK1 methylation may be associated with susceptibility to AS. In addition, DNA methylation levels of DKK1 were negatively correlated with the level of inflammation in AS patients.
近年来,甲基化修饰对与强直性脊柱炎(AS)相关的 Dickkopf-1(DKK1)的影响仍不清楚。我们的目的是研究 DKK1 甲基化模式与转录水平与 AS 易感性之间的潜在联系。采用靶向亚硫酸氢盐测序法测量了 82 例 AS 患者和 82 例健康对照者(HCs)的 DKK1 基因甲基化水平。此外,采用实时定量转录聚合酶链反应检测了 35 例 AS 患者和 35 例 HCs 外周血单个核细胞中 DKK1 的转录水平。我们的研究表明,AS 患者的 DKK1 明显低甲基化(P<0.001)。ROC 曲线表明 DKK1 甲基化可能是一种潜在的生物标志物。结果表明,AS 患者和 HCs 之间 DKK1 转录水平的差异无统计学意义。进一步分析表明,DKK1 甲基化水平与年龄呈正相关,与 C 反应蛋白水平、中性粒细胞/淋巴细胞比值(NLR)和血小板/淋巴细胞比值(PLR)呈负相关。AS 患者 PBMC 中的 DKK1 甲基化水平明显低于 HCs,DKK1 甲基化可能与 AS 的易感性有关。此外,AS 患者 DKK1 的 DNA 甲基化水平与炎症水平呈负相关。