DNA methylation and transcriptome signatures of the FOXO1 gene in ankylosing spondylitis

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease with complex etiology. The forkhead box O (FOXO) 1 is an important transcription factor related to proliferation, homeostasis and metabolism. Notably, the involvement of methylation and the expression of mRNA in the promoter region of the FOXO1 gene in relation to AS is still not understood. A two-stage case-control study enrolled 60 AS patients and 60 healthy controls (HCs) for integrated demographic and clinical evaluation and DNA methylation profiling. Subsequently, FOXO1 mRNA expression was comparatively assessed in 30 AS patients and 30 hCs. The methylation levels of 2 islands and 10 sites in the promoter region of FOXO1 gene were significantly different between AS patients and healthy controls. The negative correlation between the mRNA expression and the methylation level of FOXO1 gene was revealed (rs = -0.624, p < .001). Subgroup analyses showed that male and HLA-B27(+) having high methylation level in AS patients (p = .008; p = .036). Moreover, the level of hypermethylation was positively correlated with the clinical features like ASDAS, and negatively correlated with LYM, MON, RDW and disease duration. DNA methylation and transcription of FOXO1 might be related to AS susceptibility and play an important role in the etiology of AS.