title: Host genetic factors, related to inflammatory response, influence the CpG island methylation status in colonic mucosa in ulcerative colitis.
abstract: BACKGROUND
  CpG island hypermethylation (CIHM) in gene promoter is frequently observed in the colonic mucosa in ulcerative colitis (UC), and is strongly involved in UC-associated colorectal carcinogenesis (CRC). The influence of common single nucleotide polymorphisms (SNPs) related to inflammatory immune response on the individual susceptibility to CIHM status in the non-neoplastic rectal mucosa in UC patients was evaluated.
  
  
  METHODS
  Ten candidate SNPs, multidrug resistance 1 (MDR1) 3435 (C>T), regulated upon activation, normal T-cell expressed and secreted (RANTES)-28 (C>G), heat-shock protein (HSP)70-2 1267 (B>A), NADPH oxidase p22PHOX 242 (C>T), Toll-like receptor (TLR)2-196 to -174 (ins >del), CD14-159 (C>T), Mannan-binding lectin (MBL)2 codon 54 (G>A), tumor necrosis factor-α(TNF-α) -857 (C>T), interleukin-1β(IL-1β)-511 (C>T), and IL-1β -31 (T>C) were genotyped in 58 UC patients without neoplastic lesions, in relation to CIHM in the rectal mucosa of three candidate CpG (p14, p16 and E-cadherin: CDH1) loci, assessed by methylation-specific-polymerase chain reaction (MSP). High CIHM was defined as two or more CpG islands methylated.
  
  
  RESULTS
  The CD14-159TT genotype held a significantly higher susceptibility to CIHM of the p16 promoter (OR=3.82, 95%CI=1.06-13.79, p=0.04) A significant association was also found between the IL-1β-31TC genotype and reduced susceptibility to high CIHM (OR=0.14, 95%CI=0.22-0.94, p=0.04). The p22PHOX 242CT genotype and MBL2 codon 54 A carrier (GA+AA) were significantly associated with a lower mean number of CIHM (p=0.029, 0.046, respectively).
  
  
  CONCLUSIONS
  CD14 -159, IL-1β-31, p22PHOX 242 and MBL2 codon 54 SNPs may influence the CIHM status in the rectal mucosa of UC patients and may therefore be substantially involved in UC-associated carcinogenesis.
authors.affiliation: 1-98 Dengakugakubo Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kmiya
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Hideto
authors.initials: H
authors.lastname: Yamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics