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

• Published in: British journal of dermatology (1951) Vol. 158; no. 5; pp. 987 - 993
• Main Authors: Chen, M., Chen, Z-Q., Cui, P-G., Yao, X., Li, Y-M., Li, A-S., Gong, J-Q., Cao, Y-H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008; Blackwell
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Dermatology; DNA Methylation; Epidermis; Female; gene methylation; Genes, p16; Humans; Male; Medical sciences; Middle Aged; mRNA; p16INK4a; Promoter Regions, Genetic - genetics; psoriasis; Psoriasis - genetics; Psoriasis. Parapsoriasis. Lichen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Promoter; Skin disease; Messenger RNA; Psoriasis; Dermatology; Epidermis; mRNA; Methylation; p16INK4a; Tumor suppressor gene; gene methylation
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2008.08505.x

Summary 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.