Differences of RUNX2 gene promoter methylation and transcription level in ankylosing spondylitis
Feier Wang and Yuting Chen contributed equally to this work and should be considered co-first author.
Abstract
Background and Objective
Ankylosing spondylitis is a refractory immune disease that seriously affects the life and work of patients. Epigenetic modifications, especially DNA methylation, have become a research hotspot in complex diseases. We aim to explore the changes in runt-related transcription factor 2 (RUNX2) gene promoter methylation and transcription level in AS.
Method
We detected the RUNX2 gene promoter methylation in 83 AS patients and 83 healthy controls (HCs), then inspected the mRNA difference of RUNX2 between 30 AS patients and 30 HCs by the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
Results
The RUNX2 gene promoter was hypomethylated in AS patients compared to HCs (p < .001). The research involved 4 CpG regions and 74 CpG sites of RUNX2, of which CpG-2, CpG-4 regions, and 18 CpG sites have been differentially methylated. The CpG-4 island methylation was negatively correlated with C-reactive protein (p < .05) in AS patients. In the qRT-PCR validation phase, the mRNA level of RUNX2 in AS patients was significantly higher than HCs (p < .05), and in AS patients who were treated with biologics, the methylation level of CpG-2 island showed a negative correlation to mRNA (p < .05). ROC results indicated that RUNX2 methylation and its transcription level have good potential to distinguish AS patients from HCs.
Conclusion
The RUNX2 gene promoter was hypomethylated in AS patients. Meanwhile, the qRT-PCR verified the up-regulated expression on the transcription level, suggesting the abnormal methylation of RUNX2 contributes to the pathogenesis of AS.
CONFLICT OF INTEREST STATEMENT
All authors disclosed no relevant relationship.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
