Leukocyte Telomere Length in Patients with Transfusion-Dependent Thalassemia

Abstract Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ³18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72±0.18 and 0.99±0.25, respectively (p <0.0001). There was a significant correlation between the T/S ratio and age (p = 0.0002), and hemoglobin level (p = 0.044). There was no correlation between telomere length and other factors. Conclusions: Our study showed that TDT patients had shorter leukocyte telomere length compared with controls. Leukocyte telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

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Telomere Length in Patients with Transfusion-Dependent Thalassemia

10.21203/rs.2.17677/v3 ◽

2020 ◽

Author(s):

Nithita Nanthatanti ◽

Adisak Tantiworawit ◽

Pokpong Piriyakhuntorn ◽

Thanawat Rattanathammethee ◽

Sasinee Hantrakool ◽

...

Keyword(s):

Iron Overload ◽

Telomere Length ◽

Major Complication ◽

Single Copy ◽

Cross Sectional Study ◽

Hemoglobin Level ◽

Cellular Damage ◽

Repair System ◽

Leukocyte Telomere Length ◽

Cross Sectional

Abstract Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin level was 7.1±1.07 g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72±0.18 and 0.99±0.25, respectively (p <0.0001). There was a significant correlation between the T/S ratio and age (p = 0.0002), and hemoglobin level (p = 0.044). There was no correlation between telomere length and other factors. Conclusions: Our study showed that TDT patients had shorter leukocyte telomere length compared with controls. Leukocyte telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

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Telomere Length in Patients with Transfusion-Dependent Thalassemia

10.21203/rs.2.17677/v1 ◽

2019 ◽

Author(s):

Nithita Nanthatanti ◽

Adisak Tantiworawit ◽

Pokpong Piriyakhuntorn ◽

Thanawat Rattanathammethee ◽

Sasinee Hantrakool ◽

...

Keyword(s):

Iron Overload ◽

Telomere Length ◽

Major Complication ◽

Cross Sectional Study ◽

Cellular Damage ◽

Repair System ◽

Cross Sectional ◽

Chronic Anemia ◽

Real Time Quantitative Pcr ◽

End Caps

Abstract Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non transfusion-dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ³18 years. Telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin (Hb) was 7.1 (± 1.07) g/dL. The mean telomeric terminal restriction fragment length (TRFL) of patients with TDT and the controls was 6.11 (± 0.61) kb and 6.79 (± 0.84) kb, respectively (p <0.0001). There was a significant correlation between TRFL and age (p =0.0002), and Hb (p=0.044). There was no correlation of telomere length with other factors. Conclusions: Our study showed that TDT patients had shorter telomere length compared with controls. Telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

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Telomere Length in Patients with Transfusion-Dependent Thalassemia

10.21203/rs.2.17677/v2 ◽

2020 ◽

Author(s):

Nithita Nanthatanti ◽

Adisak Tantiworawit ◽

Pokpong Piriyakhuntorn ◽

Thanawat Rattanathammethee ◽

Sasinee Hantrakool ◽

...

Keyword(s):

Iron Overload ◽

Telomere Length ◽

Major Complication ◽

Cross Sectional Study ◽

Cellular Damage ◽

Repair System ◽

Cross Sectional ◽

Chronic Anemia ◽

Real Time Quantitative Pcr ◽

End Caps

Abstract Background: Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods: This research aimed to study the telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ³18 years. Telomere length was measured by real-time quantitative PCR. Results: Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin (Hb) was 7.1 (± 1.07) g/dL. The mean telomere terminal restriction fragment (TRF) length of patients with TDT and the controls was 6.11 (± 0.61) kb and 6.79 (± 0.84) kb, respectively (p <0.0001). There was a significant correlation between telomere TRF length and age (p =0.0002), and Hb (p=0.044). There was no correlation of telomere length with other factors. Conclusions: Our study showed that TDT patients had shorter telomere length compared with controls. Telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

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Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults

PLoS Medicine ◽

10.1371/journal.pmed.1002188 ◽

2016 ◽

Vol 13 (11) ◽

pp. e1002188 ◽

Cited By ~ 60

Author(s):

David H. Rehkopf ◽

Belinda L. Needham ◽

Jue Lin ◽

Elizabeth H. Blackburn ◽

Ami R. Zota ◽

...

Keyword(s):

Cardiovascular Disease ◽

Telomere Length ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cross Sectional Study ◽

Leukocyte Telomere Length ◽

Sectional Study ◽

Cross Sectional

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Faculty Opinions recommendation of Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727041882.793531842 ◽

2017 ◽

Author(s):

Jing-Dong Jackie Han

Keyword(s):

Cardiovascular Disease ◽

Telomere Length ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cross Sectional Study ◽

Leukocyte Telomere Length ◽

Sectional Study ◽

Cross Sectional

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Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7–9 year old rural Gambian children

Scientific Reports ◽

10.1038/s41598-020-66729-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kim Maasen ◽

Philip T. James ◽

Andrew M. Prentice ◽

Sophie E. Moore ◽

Caroline H. Fall ◽

...

Keyword(s):

Telomere Length ◽

Cross Sectional Study ◽

Leukocyte Telomere Length ◽

Sectional Study ◽

Cross Sectional

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Leukocyte Telomere Length Is Not Reduced in Children and Adults with Cystic Fibrosis but Associates with Clinical Characteristics—A Cross-Sectional Study

Journal of Clinical Medicine ◽

10.3390/jcm10040590 ◽

2021 ◽

Vol 10 (4) ◽

pp. 590

Author(s):

Aleksandra Glapa-Nowak ◽

Shivaprakash Jagalur Mutt ◽

Aleksandra Lisowska ◽

Ewa Sapiejka ◽

Joanna Goździk-Spychalska ◽

...

Keyword(s):

Cystic Fibrosis ◽

Telomere Length ◽

Clinical Characteristics ◽

Inhaled Corticosteroids ◽

Cross Sectional Study ◽

Length Variation ◽

Leukocyte Telomere Length ◽

Cross Sectional ◽

Adult Status ◽

The Moment

We hypothezied that telomere length is considerably altered in cystic fibrosis (CF) patients compared to healthy subjects (HS), and that leukocyte telomere length variation reflects the severity of CF. Relative telomere length (RTL) was assessed by qPCR in 70 children aged 5–10 (34 CF; 36 HS) and 114 adults aged 18–45 (53 CF; 61 HS). Telomere length was similar in CF and HS (median (interquartile range): 0.799 (0.686–0.950) vs. 0.831 (0.707–0.986); p = 0.5283) both in children and adults. In adults, women had longer telomeres than men (0.805 (0.715–0.931) vs. 0.703 (0.574–0.790); p = 0.0002). Patients treated with inhaled corticosteroids had a shorter RTL compared to those without steroid therapy (0.765 (0.664–0.910) vs. 0.943 (0.813–1.191); p = 0.0007) and this finding remained significant after adjusting for gender, age, BMI, and child/adult status (p = 0.0003). Shorter telomeres were independently associated with the presence of comorbidities (0.763 (0.643–0.905) vs. 0.950 (0.783–1.130); p = 0.0006) and antibiotic treatment at the moment of blood sampling (0.762 (0.648–0.908) vs. 0.832 (0.748–1.129); p = 0.0172). RTL correlated with number of multiple-day hospitalizations (rho = −0.251; p = 0.0239), as well as number of hospitalization days (rho = −0.279; p = 0.0113). Leukocyte RTL in children and adults with CF was not shorter than in healthy controls, and did not seem to have any potential as a predictor of CF survival. However, it inversely associated with the investigated clinical characteristics.

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Leukocyte telomere length is associated with iron overload in male adults with hereditary hemochromatosis

Bioscience Reports ◽

10.1042/bsr20201916 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Maximilino Martín ◽

Andrea Millan ◽

Florencia Ferraro ◽

Walter F. Tetzlaff ◽

Ezequiel Lozano Chiappe ◽

...

Keyword(s):

Iron Overload ◽

Telomere Length ◽

Linear Trend ◽

Iron Status ◽

Hereditary Hemochromatosis ◽

Cellular Aging ◽

Cellular Damage ◽

Cross Sectional ◽

Ferritin Concentration ◽

Telomere Attrition

Abstract Background: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality. Aim: To evaluate the relationship between ATL and IO in patients with HH. Methods: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR. Results: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6–14), without IO: 13 (9–20), and controls: 19 (15–25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05). Discussion: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

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