Subgroup and correlation analyses and of ERAP1methylation
ERAP1 was known to play roles cooperated with HLA-B27 in AS. Nevertheless, we found that the methylation levels of ERAP1_1 and ERAP1_2 islands of HLA-B27 positive patients were not significantly different from HLA-B27 negative patients (Z = -0.180, P = 0.857). The known environmental factors associated with DNA methylation of smoking (Z = -0.268, P = 0.789) and alcohol use (Z = -0.969, P = 0.332) were also reported not associated with the methylation level in AS patients detailed in Table 4. Among the demographic and clinical factors, we found that patients with family history have lower methylation level of ERAP1_1 island (Z = -2.258, P = 0.024). Non-steroidal anti-inflammatory drugs (NSAIDs) use was significantly associated with higher methylation level of ERA1_2 island (Z = -2.113, P = 0.035), but not any medication use history (Z = -0.605, P = 0.545). As to the variates about disease activity and function, we also found that the methylation level of ERAP1_1 island was significant associated with global back pain (rs = 0.502, P = 0.002) of AS patiens. X-ray classification of sacroiliac joint (rs = 0.548, P = 0.018) was associated with the methylation level of ERAP1_2 island (Table 5).