Accelerated telomere attrition in children and teenagers with alpha(1)-antitrypsin deficiency
Por:
Escribano A, Pastor S, Reula A, Castillo S, Vicente S, Sanz F, Casas F, Torres M, Fernández-Fabrellas E, Codoñer-Franch P and Dasí F
Publicada:
1 ago 2016
Ahead of Print:
7 jul 2016
Resumen:
Numerous studies have shown that oxidative stress accelerates telomere
shortening in several lung pathologies. Since oxidative stress is
involved in the pathophysiology of alpha(1)-antitrypsin deficiency
(AATD), we hypothesised that telomere shortening would be accelerated in
AATD patients. This study aimed to assess telomere length in AATD
patients and to study its association with alpha(1)-antitrypsin
phenotypes.
Telomere length, telomerase activity, telomerase reverse transcriptase
(hTERT) expression and biomarkers of oxidative stress were measured in
62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18
controls (aged 3-16 years).
Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD
patients have significantly shorter telomeres and increased oxidative
stress than controls. Correlation studies indicate that telomere length
was related to oxidative stress markers in AATD patients. Multiple
hypothesis testing revealed an association between telomere length,
telomerase activity, hTERT expression and AATD phenotypes; high-risk
patients showed shorter telomeres, lower hTERT expression and decreased
telomerase activity than intermediate-risk and low-risk patients.
AATD patients show evidence of increased oxidative stress leading to
telomere attrition. An association between telomere and
alpha(1)-antitrypsin phenotypes is observed suggesting that telomere
length could be a promising biomarker for AATD disease progression.
Filiaciones:
Escribano A:
Dept of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain These authors contributed equally
Pastor S:
Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Dept of Physiology, School of Medicine, University of Valencia, Valencia, Spain These authors contributed equally
Reula A:
Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Dept of Physiology, School of Medicine, University of Valencia, Valencia, Spain
Castillo S:
Dept of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
Vicente S:
Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
Sanz F:
Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
Casas F:
Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain Pulmonology Unit, Hospital Universitario San Cecilio de Granada, Granada, Spain
Torres M:
Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain Pulmonology Unit, Complexo Universitario de Vigo, Pontevedra, Spain
Fernández-Fabrellas E:
Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
:
Dept of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Unit, Hospital Universitario Dr. Peset Valencia, Valencia, Spain
Dasí F:
Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain Dept of Physiology, School of Medicine, University of Valencia, Valencia, Spain
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