title: Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.
abstract: Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Laish
authors.forename: Batya
authors.initials: B
authors.lastname: Mannasse-Green
authors.forename: Ruth
authors.initials: R
authors.lastname: Hadary
authors.forename: Tal
authors.initials: T
authors.lastname: Biron-Shental
authors.forename: Fred M
authors.initials: FM
authors.lastname: Konikoff
authors.forename: Aliza
authors.initials: A
authors.lastname: Amiel
authors.forename: Yona
authors.initials: Y
authors.lastname: Kitay-Cohen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000235:genetics; D018450:Disease Progression; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008103:Liver Cirrhosis / Q000151:congenital* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics; D059506:Telomere Shortening / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase