Promoter methylation of protease-activated receptor (PAR2) is associated with severe clinical phenotypes of ulcerative colitis (UC).
Tryptase acting at protease-activated receptor 2 (PAR2) contributes to the pathogenesis of Inflammatory bowel diseases (IBDs). DNA methylation has been shown to be an important mechanism in gene silencing. We attempted to clarify the relationship between the promoter methylation of PAR2 and ulcerative colitis (UC). 84 UC patients enrolled in the study. UC patients were classified by disease behavior, severity and extent of disease. For rectal inflammatory mucosal specimens from all the patients, and normal terminal ileum from 23 patients, promoter methylation of PAR2 gene was quantified by digital densitographic analysis following to methylation-specific polymerase chain reaction (MSP). The mean methylation levels of the PAR2 gene in all 84 subjects was 38.4 +/- 19.6%. Although mean methylation levels in rectal inflammatory mucosa, and paired normal terminal ileum did not vary, methylation levels of PAR2 gene was significantly higher in total colitis than rectal colitis (total colitis vs. rectal colitis; 42.9 +/- 19.6% vs. 34.5 +/- 18.9%, P = 0.046). The higher methylation levels were also associated with Steroid-dependent (P = 0.002) and refractory (P = 0.007) UC. Our data suggest that PAR2 methylation status in rectal mucosa correlates with more severe disease phenotypes of UC.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
T
Nakamura
Masakatsu
M
Yamashita
Hiromi
H
Yoshioka
Daisuke
D
Okubo
Masaaki
M
Maruyama
Naoko
N
Kamano
Toshiaki
T
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Nakagawa
Yoshihito
Y
Nagasaka
Mitsuo
M
Iwata
Masami
M
Takahama
Kazuya
K
Watanabe
Makoto
M
Nakano
Hiroshi
H
Hirata
Ichiro
I
Arisawa
Tomiyasu
T
D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D044464:Receptor, PAR-2 / Q000235:genetics*
D044464:Receptor, PAR-2