title: Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use.
abstract: Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values <0.01) and CDH1 methylation (p = 0.0002). In H. pylori-negative subjects, NSAID users presented significantly shorter telomere length than nonusers (p = 0.028). Shorter telomere length was observed in duodenal and gastric ulcer patients compared with non-ulcer subjects among NSAID users. Telomere shortening is closely associated with severity of H. pylori-induced gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan. tomomiccyu@yahoo.co.jp.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Aichi, Toyoake, 470-1192, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D005756:Gastritis / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology*; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000097:blood; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016615:Telomere / Q000187:drug effects / Q000235:genetics*; D059506:Telomere Shortening / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D010435:Pepsinogens
keywords: DNA methylation; Gastric mucosa; H. pylori; NSAIDs; Telomere length; Ulcer diseases