Abstract
Summary Objective: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is
known to participate in the pathogenesis of ankylosing spondylitis (AS)
cooperated with HLA-B27. This study aimed to evaluate the relationship
between promoter methylation and mRNA levels of ERAP1 and AS. Methods:
The DNA methylation level of 100 AS patients and 100 health controls
(HCs) were tested using targeted bisulfite sequencing assay. Besides,
the mRNA level of 20 AS patients and HCs was measured used quantitative
real-time reverse transcription-polymerase chain reaction to verify the
results of DNA methylation. Results: The methylation levels of two CpG
islands containing 31 loci in ERAP1 promoter were measured. ERAP1_1 (P
< 0.001) and ERAP1_2 (P < 0.001) islands were
significantly hyperrmethylated in AS patients compared with healthy
controls. Correspondingly, the mRNA level was significantly lower in AS
patients. The ROC curve analysis reported the sensitivity, specificity
and area under curve were 0.717, 0.737 and 0.779 of differential
methylated CpG loci of ERAP1 for AS diagnosis. Besides, we also found
that the methylation level was associated with the family history,
non-steroidal anti-inflammatory drugs use, X-ray classification and
clinical manifestations. Conclusions: Our study demonstrated that the
ERAP1 gene is significantly hypermethylated in AS patients, which is
verified by the lower mRNA level of AS patients. Our findings suggested
that aberrant methylation of ERAP1 promoter may take part in the
pathogenesis of AS and can be considered as diagnostic tool and
therapeutic target of AS.