Host genetic factors, related to inflammatory response, influence the CpG island methylation status in colonic mucosa in ulcerative colitis

Tomomitsu Tahara, Tomoyuki Shibata, Masakatsu Nakamura, Masaaki Okubo, Hiromi Yamashita, Daisuke Yoshioka, Joh Yonemura, Yoshio Kmiya, Takamitsu Ishizuka, Hiroshi Fujita, Mitsuo Nagasaka, Hideto Yamada, Ichiro Hirata, Tomiyasu Arisawa

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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. Patients and 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). Conclusion: CD14 -159, 1L-Iβ-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.

Original languageEnglish
Pages (from-to)933-938
Number of pages6
JournalAnticancer research
Volume31
Issue number3
Publication statusPublished - 01-03-2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Tahara, T., Shibata, T., Nakamura, M., Okubo, M., Yamashita, H., Yoshioka, D., Yonemura, J., Kmiya, Y., Ishizuka, T., Fujita, H., Nagasaka, M., Yamada, H., Hirata, I., & Arisawa, T. (2011). Host genetic factors, related to inflammatory response, influence the CpG island methylation status in colonic mucosa in ulcerative colitis. Anticancer research, 31(3), 933-938.