NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects

Tomiyasu Arisawa, Tomomitsu Tahara, Hisakazu Shiroeda, Hideto Yamada, Tomoe Nomura, Ranji Hayashi, Takashi Saito, Tomoki Fukuyama, Toshimi Otsuka, Masakatsu Nakamura, Nobuyuki Toshikuni, Mutsumi Tsuchishima, Tomoyuki Shibata

研究成果: Article

6 引用 (Scopus)

抄録

CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of NF-κB in the inflammatory response to H. pylori colonization has been indicated. We investigated the influence of NFKB1 polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the aberrant gene methylation under H. pylori infection. Gastric mucosal samples were obtained from sub-subjects without malignancies. Methylation status of genes (p14 ARF, p16 INK4a, DAPK and CDH1) was determined by methylation-specific PCR (MSP). The genotyping of NFKB1 was performed by PCR-SSCP. There was a strong allelic association between rs28362491 and rs72696119, and all H. pylori-infected -94 del/del homozygotes had a -449 GG genotype. The -94 del/del homozygosity was significantly associated with risk for development of CpG island high methylation (CIHM) (two or more gene methylations), especially DAPK and CDH1 methylations, and the number of methylated genes was significantly higher in -94 del/del homozygotes than in ins/del and ins/ins (ins carrier) H. pylori-infected elder subjects. In addition, this methylated gene number was significantly increased with age in H. pylori-infected del/del homozygotes, but not in infected ins carriers. Furthermore, the inflammation score was significantly higher in H. pylori-infected del/del homozygotes compared to ins carriers. NFKB1 -94 ins/del ATTG polymorphism (rs28362491) was significantly associated with the increased risk for the development of age-related gene methylation in non-cancerous gastric mucosa under H. pylori-induced inflammation.

元の言語English
ページ(範囲)255-262
ページ数8
ジャーナルInternational Journal of Molecular Medicine
30
発行部数2
DOI
出版物ステータスPublished - 01-08-2012

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Helicobacter pylori
Methylation
Homozygote
Genes
CpG Islands
Tumor Suppressor Protein p14ARF
Inflammation
Single-Stranded Conformational Polymorphism
Polymerase Chain Reaction
Helicobacter Infections
Gene Silencing
Gastric Mucosa
Stomach
Genotype
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Shiroeda, Hisakazu ; Yamada, Hideto ; Nomura, Tomoe ; Hayashi, Ranji ; Saito, Takashi ; Fukuyama, Tomoki ; Otsuka, Toshimi ; Nakamura, Masakatsu ; Toshikuni, Nobuyuki ; Tsuchishima, Mutsumi ; Shibata, Tomoyuki. / NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects. :: International Journal of Molecular Medicine. 2012 ; 巻 30, 番号 2. pp. 255-262.
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title = "NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects",
abstract = "CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of NF-κB in the inflammatory response to H. pylori colonization has been indicated. We investigated the influence of NFKB1 polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the aberrant gene methylation under H. pylori infection. Gastric mucosal samples were obtained from sub-subjects without malignancies. Methylation status of genes (p14 ARF, p16 INK4a, DAPK and CDH1) was determined by methylation-specific PCR (MSP). The genotyping of NFKB1 was performed by PCR-SSCP. There was a strong allelic association between rs28362491 and rs72696119, and all H. pylori-infected -94 del/del homozygotes had a -449 GG genotype. The -94 del/del homozygosity was significantly associated with risk for development of CpG island high methylation (CIHM) (two or more gene methylations), especially DAPK and CDH1 methylations, and the number of methylated genes was significantly higher in -94 del/del homozygotes than in ins/del and ins/ins (ins carrier) H. pylori-infected elder subjects. In addition, this methylated gene number was significantly increased with age in H. pylori-infected del/del homozygotes, but not in infected ins carriers. Furthermore, the inflammation score was significantly higher in H. pylori-infected del/del homozygotes compared to ins carriers. NFKB1 -94 ins/del ATTG polymorphism (rs28362491) was significantly associated with the increased risk for the development of age-related gene methylation in non-cancerous gastric mucosa under H. pylori-induced inflammation.",
author = "Tomiyasu Arisawa and Tomomitsu Tahara and Hisakazu Shiroeda and Hideto Yamada and Tomoe Nomura and Ranji Hayashi and Takashi Saito and Tomoki Fukuyama and Toshimi Otsuka and Masakatsu Nakamura and Nobuyuki Toshikuni and Mutsumi Tsuchishima and Tomoyuki Shibata",
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Arisawa, T, Tahara, T, Shiroeda, H, Yamada, H, Nomura, T, Hayashi, R, Saito, T, Fukuyama, T, Otsuka, T, Nakamura, M, Toshikuni, N, Tsuchishima, M & Shibata, T 2012, 'NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects', International Journal of Molecular Medicine, 巻. 30, 番号 2, pp. 255-262. https://doi.org/10.3892/ijmm.2012.1004

NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Shiroeda, Hisakazu; Yamada, Hideto; Nomura, Tomoe; Hayashi, Ranji; Saito, Takashi; Fukuyama, Tomoki; Otsuka, Toshimi; Nakamura, Masakatsu; Toshikuni, Nobuyuki; Tsuchishima, Mutsumi; Shibata, Tomoyuki.

:: International Journal of Molecular Medicine, 巻 30, 番号 2, 01.08.2012, p. 255-262.

研究成果: Article

TY - JOUR

T1 - NFKB1 polymorphism is associated with age-related gene methylation in Helicobacter pylori-infected subjects

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Shiroeda, Hisakazu

AU - Yamada, Hideto

AU - Nomura, Tomoe

AU - Hayashi, Ranji

AU - Saito, Takashi

AU - Fukuyama, Tomoki

AU - Otsuka, Toshimi

AU - Nakamura, Masakatsu

AU - Toshikuni, Nobuyuki

AU - Tsuchishima, Mutsumi

AU - Shibata, Tomoyuki

PY - 2012/8/1

Y1 - 2012/8/1

N2 - CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of NF-κB in the inflammatory response to H. pylori colonization has been indicated. We investigated the influence of NFKB1 polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the aberrant gene methylation under H. pylori infection. Gastric mucosal samples were obtained from sub-subjects without malignancies. Methylation status of genes (p14 ARF, p16 INK4a, DAPK and CDH1) was determined by methylation-specific PCR (MSP). The genotyping of NFKB1 was performed by PCR-SSCP. There was a strong allelic association between rs28362491 and rs72696119, and all H. pylori-infected -94 del/del homozygotes had a -449 GG genotype. The -94 del/del homozygosity was significantly associated with risk for development of CpG island high methylation (CIHM) (two or more gene methylations), especially DAPK and CDH1 methylations, and the number of methylated genes was significantly higher in -94 del/del homozygotes than in ins/del and ins/ins (ins carrier) H. pylori-infected elder subjects. In addition, this methylated gene number was significantly increased with age in H. pylori-infected del/del homozygotes, but not in infected ins carriers. Furthermore, the inflammation score was significantly higher in H. pylori-infected del/del homozygotes compared to ins carriers. NFKB1 -94 ins/del ATTG polymorphism (rs28362491) was significantly associated with the increased risk for the development of age-related gene methylation in non-cancerous gastric mucosa under H. pylori-induced inflammation.

AB - CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of NF-κB in the inflammatory response to H. pylori colonization has been indicated. We investigated the influence of NFKB1 polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the aberrant gene methylation under H. pylori infection. Gastric mucosal samples were obtained from sub-subjects without malignancies. Methylation status of genes (p14 ARF, p16 INK4a, DAPK and CDH1) was determined by methylation-specific PCR (MSP). The genotyping of NFKB1 was performed by PCR-SSCP. There was a strong allelic association between rs28362491 and rs72696119, and all H. pylori-infected -94 del/del homozygotes had a -449 GG genotype. The -94 del/del homozygosity was significantly associated with risk for development of CpG island high methylation (CIHM) (two or more gene methylations), especially DAPK and CDH1 methylations, and the number of methylated genes was significantly higher in -94 del/del homozygotes than in ins/del and ins/ins (ins carrier) H. pylori-infected elder subjects. In addition, this methylated gene number was significantly increased with age in H. pylori-infected del/del homozygotes, but not in infected ins carriers. Furthermore, the inflammation score was significantly higher in H. pylori-infected del/del homozygotes compared to ins carriers. NFKB1 -94 ins/del ATTG polymorphism (rs28362491) was significantly associated with the increased risk for the development of age-related gene methylation in non-cancerous gastric mucosa under H. pylori-induced inflammation.

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