Effect of MDR1 gene promoter methylation in patients with ulcerative colitis

  • Authors:
    • Tomomitsu Tahara
    • Tomoyuki Shibata
    • Masakatsu Nakamura
    • Hiromi Yamashita
    • Daisuke Yoshioka
    • Masaaki Okubo
    • Naoko Maruyama
    • Toshiaki Kamano
    • Yoshio Kamiya
    • Yoshihito Nakagawa
    • Hiroshi Fujita
    • Mitsuo Nagasaka
    • Masami Iwata
    • Kazuya Takahama
    • Makoto Watanabe
    • Ichiro Hirata
    • Tomiyasu Arisawa
  • Corresponding author:
  • View Affiliations

  • Published online on: Wednesday, April 1, 2009
  • Pages: 521-527
  • DOI: 10.3892/ijmm_00000160

Abstract

Altered MDR1 expression and/or function contribute to the pathogenesis of inflammatory bowel disease (IBD). DNA methylation was shown as an important mechanism in gene silencing. We investigated DNA methylation of the MDR1 gene in ulcerative colitis (UC) and its relation to MDR1 C3435T genotypes. Eighty-three UC patients were enrolled. Methylation of MDR1 promoter was determined by methylation specific polymerase (MSP) for rectal inflammatory mucosa from all patients and normal terminal ileum from 17 patients. Promoter methylation of MDR1 gene was also quantified by digital densitographic analysis following MSP. MDR1 methylation was detected in 51 (61.4%) out of 83 patients in rectal inflammatory mucosa. Mean methylation level of MDR1 gene in rectal inflammatory mucosa was significantly higher than in normal terminal ileum (p=0.021). MDR1 methylation occurred more frequently in total colitis, and total + left side colitis, compared to rectal colitis (p=0.001, 0.013, respectively). Higher methylation levels were also associated with chronic continuous type (p=0.034) and earlier onset of disease (p=0.038). The 3435 CC+CT genotype of MDR1 was associated with more than 6-fold increased risk of MDR1 methylation, especially in UC patients with 9 years and shorter duration. Both frequency and level of MDR1 methylation were higher in UC onset at younger or in middle age with the same genotype. MDR1 methylation frequently occurred in inflammatory rectal mucosa from UC patients and was influenced by MDR1 C3435T polymorphism, especially in patients with shorter duration and younger onset.
Journal Cover

April 2009
Volume 23 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

2013 Impact Factor: 1.88
Ranked #27/122 Medicine Research and Experimental
(total number of cites)

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APA
Tahara, T., Shibata, T., Nakamura, M., Yamashita, H., Yoshioka, D., Okubo, M. ... Arisawa, T. (2009). Effect of MDR1 gene promoter methylation in patients with ulcerative colitis. International Journal of Molecular Medicine, 23, 521-527. http://dx.doi.org/10.3892/ijmm_00000160
MLA
Tahara, T., Shibata, T., Nakamura, M., Yamashita, H., Yoshioka, D., Okubo, M., Maruyama, N., Kamano, T., Kamiya, Y., Nakagawa, Y., Fujita, H., Nagasaka, M., Iwata, M., Takahama, K., Watanabe, M., Hirata, I., Arisawa, T."Effect of MDR1 gene promoter methylation in patients with ulcerative colitis". International Journal of Molecular Medicine 23.4 (2009): 521-527.
Chicago
Tahara, T., Shibata, T., Nakamura, M., Yamashita, H., Yoshioka, D., Okubo, M., Maruyama, N., Kamano, T., Kamiya, Y., Nakagawa, Y., Fujita, H., Nagasaka, M., Iwata, M., Takahama, K., Watanabe, M., Hirata, I., Arisawa, T."Effect of MDR1 gene promoter methylation in patients with ulcerative colitis". International Journal of Molecular Medicine 23, no. 4 (2009): 521-527. http://dx.doi.org/10.3892/ijmm_00000160