The methylation pattern of p16INK4a gene promoter in psoriatic epidermis and its clinical significance.

Background: Alteration of the p16INK4a gene by epigenetic changes has been described in some hyperproliferative skin diseases, but its importance in psoriasis has not yet been established.

Objectives: To investigate the methylation status of the p16INK4a gene in psoriatic epidermis, its clinical significance and the possible epigenetic mechanisms of psoriasis.

Methods: DNA and RNA specimens were obtained from the lesional epidermis of 56 patients with plaque psoriasis. Methylation-specific polymerase chain reaction (PCR) and DNA sequencing were used to detect the density and sites of methylation in the p16INK4a promoter region. The reverse transcription-PCR technique was applied to detect the mRNA expression of p16INK4a.

Results: p16INK4a gene promoter methylation was shown in 17 of 56 (30%) patients with psoriasis. Psoriasis Area and Severity Index scores in patients showing methylation were higher than in those who did not (P<0.05). The mRNA expression level of p16INK4a in the methylated group was significantly lower than in the unmethylated group (t=2.515, P=0.015). In the methylated group, about 50% of the CpG islands were methylated in the promoter region.

Conclusions: Overall, methylation of the p16INK4a gene promoter is found in psoriatic epidermis, which is associated with the mRNA level of p16INK4a expression and activity of the disease. These data indicate that methylation of the p16INK4a promoter may play a potential role in the pathogenesis of psoriasis.