title: Accelerated telomere shortening in β-thalassemia/HbE patients.
abstract: β-Thalassemia/HbE disease is caused by a defective β-globin synthesis that leads to accumulation of excess unbound α-globins, and consequently oxidative stress, ineffective erythropoiesis and chronic anemia. Cell replication and oxidative stress are factors contributing to erosion of telomeres responsible for maintaining genomic stability and cell replication capability. In this study, the rate of telomere shortening in β-thalassemia/HbE patients was compared to the rate of telomere shortening in normal individuals. Telomere length was determined from peripheral blood mononuclear cells of 43 β-thalassemia/HbE patients and 22 normal controls using Flow-FISH analysis. The telomere length was shown to be age-dependent in normal group (rs = 0.715, P = 0.002), whereas severity-dependent telomere shortening was observed in the patients. The telomere length of patients who had severe clinical symptoms (10.07 ± 2.15%) was shorter than that of patients who showed mild symptoms (15.59 ± 2.27%), moderate symptoms (14.50 ± 1.41%) and those in the normal group (14.75 ± 3.11%, P < 0.05). Additionally, reticulocyte count and oxidative stress were correlated with telomere length. This indicates that increased oxidative stress and markedly enhanced erythropoiesis in β-thalassemia/HbE patients leads to accelerated telomere erosion in clinically severe patients.
authors: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Pornthip
authors: P
authors: Chaichompoo
authors: Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Kovit
authors: K
authors: Pattanapanyasat
authors: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors: Pranee
authors: P
authors: Winichagoon
authors: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors: Suthat
authors: S
authors: Fucharoen
authors: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: saovaros.sva@mahidol.ac.th.
authors: Saovaros
authors: S
authors: Svasti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D004909:Erythrocyte Indices; D005260:Female; D005838:Genotype; D006446:Hemoglobin E / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D045262:Reticulocytosis; D012720:Severity of Illness Index; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D055542:alpha-Globins; D055544:beta-Globins; D006446:Hemoglobin E; D019098:Telomerase
keywords: Flow-FISH; Oxidative stress; Telomerase; Telomere; Thalassemia