Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis

Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their imp...

ver descrição completa

Detalhes bibliográficos
Autores: López-Campos Bodineau, José Luis, García Tamayo, Pedro, Girón, Maria Victoria, Delgado Pecellín, Isabel, Olveira, Gabriel, Carrasco, Laura, Quintana-Gallego, Esther
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/178295
Acesso em linha:https://hdl.handle.net/11441/178295
https://doi.org/10.3390/jcm14196789
Access Level:acceso abierto
Palavra-chave:Alpha1 antitrypsin deficiency
Cystic fibrosis
Genetic studies
Prevalence
Screening
id ES_aa2be7cc5e77dd02a304f8e9adb4912e
oai_identifier_str oai:idus.us.es:11441/178295
network_acronym_str ES
network_name_str España
repository_id_str
spelling Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosisLópez-Campos Bodineau, José LuisGarcía Tamayo, PedroGirón, Maria VictoriaDelgado Pecellín, IsabelOlveira, GabrielCarrasco, LauraQuintana-Gallego, EstherAlpha1 antitrypsin deficiencyCystic fibrosisGenetic studiesPrevalenceScreeningBackground: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies.MDPIMedicinaFarmacología, Pediatría y Radiología2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/178295https://doi.org/10.3390/jcm14196789reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of clinical medicine, 14 (19), 6789.https://www.mdpi.com/2077-0383/14/19/6789info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1782952026-06-17T12:51:07Z
dc.title.none.fl_str_mv Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
title Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
spellingShingle Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
López-Campos Bodineau, José Luis
Alpha1 antitrypsin deficiency
Cystic fibrosis
Genetic studies
Prevalence
Screening
title_short Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
title_full Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
title_fullStr Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
title_full_unstemmed Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
title_sort Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
dc.creator.none.fl_str_mv López-Campos Bodineau, José Luis
García Tamayo, Pedro
Girón, Maria Victoria
Delgado Pecellín, Isabel
Olveira, Gabriel
Carrasco, Laura
Quintana-Gallego, Esther
author López-Campos Bodineau, José Luis
author_facet López-Campos Bodineau, José Luis
García Tamayo, Pedro
Girón, Maria Victoria
Delgado Pecellín, Isabel
Olveira, Gabriel
Carrasco, Laura
Quintana-Gallego, Esther
author_role author
author2 García Tamayo, Pedro
Girón, Maria Victoria
Delgado Pecellín, Isabel
Olveira, Gabriel
Carrasco, Laura
Quintana-Gallego, Esther
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
Farmacología, Pediatría y Radiología
dc.subject.none.fl_str_mv Alpha1 antitrypsin deficiency
Cystic fibrosis
Genetic studies
Prevalence
Screening
topic Alpha1 antitrypsin deficiency
Cystic fibrosis
Genetic studies
Prevalence
Screening
description Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/178295
https://doi.org/10.3390/jcm14196789
url https://hdl.handle.net/11441/178295
https://doi.org/10.3390/jcm14196789
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of clinical medicine, 14 (19), 6789.
https://www.mdpi.com/2077-0383/14/19/6789
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416139501600768
score 15,812429

Registos relacionados