Ankylosing spondylitis is associated with aberrant DNA methylation of IFN regulatory factor 8 gene promoter region.

Objectives: To investigate the role of methylation levels of the IFN regulatory factor 8 (IRF8) gene promoter in the development of ankylosing spondylitis (AS). Methods: In this study, we compared the methylation levels of the IRF8 gene promoter between 99 AS patients and 99 healthy controls using MethylTarget approach. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to compare the mRNA levels of the IRF8 gene in the other 19 AS patients and 19 healthy controls. Results: Differential methylation was found in 91 CpG sites of the IRF8 gene promoter, and 4 CpG regions were highly methylated in AS patients compared to healthy controls (p < 0.05). In the verification stage, we found that the mRNA levels of the IRF8 gene in AS patients were significantly lower than that in controls (AS 0.77 (0.39–1.74), P = 0.038). Positive correlations between methylation of the IRF8 gene and the duration of disease, BASFI, and ESR were observed in AS patients. Conclusions: We found a significant hypermethylation of the IRF8 gene promoter and a downregulation of the mRNA levels of the IRF8 gene in AS patients. This suggests that aberrant methylation of the IRF8 gene promoter may probably contribute to the development and pathogenesis of AS through regulating the expression of mRNA. [ABSTRACT FROM AUTHOR]