Effect of MDR1 gene promoter methylation in patients with ulcerative colitis

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

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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.

Original languageEnglish
Pages (from-to)521-527
Number of pages7
JournalInternational Journal of Molecular Medicine
Volume23
Issue number4
DOIs
Publication statusPublished - 03-07-2009

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Ulcerative Colitis
Methylation
Genes
Mucous Membrane
Colitis
Genotype
DNA Methylation
Ileum
Gene Silencing
Inflammatory Bowel Diseases

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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(4), 521-527. https://doi.org/10.3892/ijmm_00000160
Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Yamashita, Hiromi ; Yoshioka, Daisuke ; Okubo, Masaaki ; Maruyama, Naoko ; Kamano, Toshiaki ; Kamiya, Yoshio ; Nakagawa, Yoshihito ; Fujita, Hiroshi ; Nagasaka, Mitsuo ; Iwata, Masami ; Takahama, Kazuya ; Watanabe, Makoto ; Hirata, Ichiro ; Arisawa, Tomiyasu. / Effect of MDR1 gene promoter methylation in patients with ulcerative colitis. In: International Journal of Molecular Medicine. 2009 ; Vol. 23, No. 4. pp. 521-527.
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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 2009, 'Effect of MDR1 gene promoter methylation in patients with ulcerative colitis', International Journal of Molecular Medicine, vol. 23, no. 4, pp. 521-527. https://doi.org/10.3892/ijmm_00000160

Effect of MDR1 gene promoter methylation in patients with ulcerative colitis. / Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yamashita, Hiromi; Yoshioka, Daisuke; Okubo, Masaaki; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Nakagawa, Yoshihito; Fujita, Hiroshi; Nagasaka, Mitsuo; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Hirata, Ichiro; Arisawa, Tomiyasu.

In: International Journal of Molecular Medicine, Vol. 23, No. 4, 03.07.2009, p. 521-527.

Research output: Contribution to journalArticle

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T1 - Effect of MDR1 gene promoter methylation in patients with ulcerative colitis

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Yamashita, Hiromi

AU - Yoshioka, Daisuke

AU - Okubo, Masaaki

AU - Maruyama, Naoko

AU - Kamano, Toshiaki

AU - Kamiya, Yoshio

AU - Nakagawa, Yoshihito

AU - Fujita, Hiroshi

AU - Nagasaka, Mitsuo

AU - Iwata, Masami

AU - Takahama, Kazuya

AU - Watanabe, Makoto

AU - Hirata, Ichiro

AU - Arisawa, Tomiyasu

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N2 - 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.

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