title: Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency.
abstract: Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-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 α1-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 α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.
authors.affiliation: 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.
authors.forename: Amparo
authors.initials: A
authors.lastname: Escribano
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Pastor
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Reula
authors.affiliation: 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castillo
authors.affiliation: Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vicente
authors.affiliation: Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanz
authors.affiliation: Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain Pulmonology Unit, Hospital Universitario San Cecilio de Granada, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Casas
authors.affiliation: Spanish Registry for Alpha-1 antitrypsin Deficiency (REDAAT), Barcelona, Spain Pulmonology Unit, Complexo Universitario de Vigo, Pontevedra, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Torres
authors.affiliation: Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Fernández-Fabrellas
authors.affiliation: Dept of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Unit, Hospital Universitario Dr. Peset Valencia, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Codoñer-Franch
authors.affiliation: 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 Francisco.Dasi@uv.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D010641:Phenotype; D013147:Spirometry; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000648:ultrastructure*; D059506:Telomere Shortening; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D019098:Telomerase