Abstract
Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age=18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis.
Highlights
Psoriasis is a common chronic skin disorder that affected about 1%-3% of the world population, and the pathogenesis of psoriasis is still unclear
The frequency of promoter methylation for human leukocyte antigens (HLA)-DRB1 in psoriatic lesions was significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001), and there is no significant difference for the rate of HLADRB1 methylation between in psoriatic non-lesions and healthy controls (t = 1.046, p = 0.299) (Figure 3)
The abnormal methylation of HLA-G gene has been found in cancers [24, 25] and preeclampsia [26]; and hypermethylation of HLA-A, B, C was observed in esophageal squamous cell carcinoma (ESCC) [27]
Summary
Psoriasis is a common chronic skin disorder that affected about 1%-3% of the world population, and the pathogenesis of psoriasis is still unclear. Many studies about the association between human leukocyte antigens (HLA) and psoriasis have been reported for a long time [2, 3]. Much attention have been paid on the role of epigenetic changes (e.g. DNA methylation) in psoriasis, and the abnormal epigenetic modification of several molecules has been observed in the psoriatic lesions of patients [4, 5]; researchers still need to make greater efforts to illustrate the mechanism of how the aberrant epigenetic modifications would affect the pathogenesis of psoriasis. Human leukocyte antigen class (HLA)-DRB1 is a transmembrane heterodimer cell surface receptor with α and β chains, and each contains extracellular domains, membrane-spanning domain and a tail anchored in the cytoplasm. The expression of HLA-DRB1 is important for APCs, because HLA-DRB1 can determine the efficiency of APCs to present antigen to T cells [7]
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