title: Hypermethylation of HLA-C may be an epigenetic marker in psoriasis.
abstract: BACKGROUND
  There are no published studies that describe the DNA methylation of human leukocyte antigen class I molecules in psoriasis despite the fact that their association to disease has been known for several decades.
  
  
  OBJECTIVE
  we investigated the methylation status of HLA-A, -B and -C loci in psoriatic epidermis.
  
  
  METHODS
  The DNA and RNA specimens were obtained from the involved and uninvoled epidermis of 56 patients with plaque psoriasis and 28 healthy persons as the control group. Methylation of HLA was examined by MSP and Bisulfite sequencing. HLA-C mRNA expression was examined by Q-PCR. The severity of disease was evaluated by psoriasis area and severity index (PASI).
  
  
  RESULTS
  In psoriatic lesions and psoriatic non-lesions, the percentage of promoter methylation for HLA-B was 3.57% (2/56) and 3.57% (2/56), while it was 14.28% (8/56) and 23.21% (13/56) for HLA-C, respectively. Methylation of HLA-A was not be detected in both psoriatic lesions and non-lesions. Methylation of HLA-A, -B and -C loci was not found in healthy controls. The frequency of promoter methylation for HLA-C in the psoriatic epidermis was significantly increased compared with healthy controls (p<0.05). Interestingly, there was no significant difference in HLA-C methylation between psoriatic lesions and non-lesions (χ(2)=1.465, p=0.167), which was further confirmed by using bisulfite sequencing (t=1.958, p=0.055). HLA-C methylation was not found in healthy controls. The mean methylation rate of HLA-C in psoriatic lesions is relative to PASI score (r=0.316, p=0.018). The mean methylation rate of HLA-C in psoriatic lesions and non-lesions of the patients (onset age ≤18 years) are higher than the other patients, respectively (t=6.884, p<0.001; t=6.551, p<0.001). The mean HLA-C mRNA expression was significantly higher in psoriatic non-lesions than normal skin (t=2.895, p=0.005), while there is no significant difference between psoriatic lesions and non-lesions (t=1.966, p=0.054). The mean value of HLA-C mRNA expression is not relative to the promoter methylation of HLA-C in psoriatic lesions and non-lesions, respectively.
  
  
  CONCLUSIONS
  We first demonstrate hypermethylation of HLA-C gene in psoriatic epidermis, suggesting that HLA-C hypermethylation may be an epigenetic marker in psoriasis.
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yao
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China.
authors.forename: Chengrang
authors.initials: C
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China. Electronic address: cuipangen@126.com.
authors.forename: Pangen
authors.initials: P
authors.lastname: Cui
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, 12 Jiangwangmiao Street, Nanjing 210042, Jiangsu, China. Electronic address: wangbx@ncstdlc.org.
authors.forename: Baoxi
authors.initials: B
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation; D004817:Epidermis / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005819:Genetic Markers; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D012333:RNA, Messenger
keywords: Gene methylation; HLA; Psoriasis; mRNA