Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is associated with increased susceptibility to chronic obstructive pulmonary disease (COPD). AATD results from mutations in the SERPINA1 gene and over 500 rare mutations have been identified. Despite these findings and recommendations from ma...

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Main Authors: Dilek Karadoğan, Bettina Dreger, Lourdes Osaba, Enes Ahmetoğlu, Songül Özyurt, Bilge Yılmaz Kara, Nur Hürsoy, Tahsin Gökhan Telatar, Ünal Şahin
Format: Article
Language:English
Published: BMC 2024-12-01
Series:BMC Pulmonary Medicine
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Online Access:https://doi.org/10.1186/s12890-024-03421-y
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author Dilek Karadoğan
Bettina Dreger
Lourdes Osaba
Enes Ahmetoğlu
Songül Özyurt
Bilge Yılmaz Kara
Nur Hürsoy
Tahsin Gökhan Telatar
Ünal Şahin
author_facet Dilek Karadoğan
Bettina Dreger
Lourdes Osaba
Enes Ahmetoğlu
Songül Özyurt
Bilge Yılmaz Kara
Nur Hürsoy
Tahsin Gökhan Telatar
Ünal Şahin
author_sort Dilek Karadoğan
collection DOAJ
description Abstract Background Alpha-1 antitrypsin deficiency (AATD) is associated with increased susceptibility to chronic obstructive pulmonary disease (COPD). AATD results from mutations in the SERPINA1 gene and over 500 rare mutations have been identified. Despite these findings and recommendations from major healthcare organizations, testing of COPD patients and their family members for AATD remains inadequate. Methods We examined genotypes and clinical characteristics of COPD patients (index cases; n = 14) treated at Recep Tayyip Erdoğan University Chest Diseases Department and their relatives (n = 17). Results When index cases were compared with screened relatives positive for AATD (n = 14), index cases were older and more predominantly male than screened relatives. Both groups had extensive smoking histories. All of the index cases and one of the screened relatives had been diagnosed with COPD. Clinical characterization of the COPD cases (14 index cases; 1 screened relative) showed that they had moderate to severe COPD with pre-treatment AAT levels of 0.59 ± 0.40 g/L (mean ± SD) and a COPD Assessment Test (CAT) score of 16.0 ± 8.12. The majority of these patients (73.3%) had panlobular emphysema. Five of the patients were treated with AAT augmentation which led to a decrease in the number of COPD exacerbations. Genotyping revealed that the most common rare allele identified in this population was MPalermo (c.227_229delTCT mutation on the M1(Val213) allelic background). Conclusions More testing and research need to be done to identify the relative prevalence of rare AATD variants. Earlier identification could lead to more effective treatment of affected individuals and improvement in their quality of life.
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issn 1471-2466
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publishDate 2024-12-01
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spelling doaj-art-e4d5fe530aa24598b12f37612664eb532025-08-20T02:40:14ZengBMCBMC Pulmonary Medicine1471-24662024-12-012411810.1186/s12890-024-03421-yClinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in TürkiyeDilek Karadoğan0Bettina Dreger1Lourdes Osaba2Enes Ahmetoğlu3Songül Özyurt4Bilge Yılmaz Kara5Nur Hürsoy6Tahsin Gökhan Telatar7Ünal Şahin8School of Medicine, Department of Chest Diseases, Recep Tayyip Erdoğan UniversityPulmonology Medical Affairs, Grifols Deutschland GmbHProgenika Biopharma, a Grifols companySchool of Medicine, Department of Chest Diseases, Recep Tayyip Erdoğan UniversitySchool of Medicine, Department of Chest Diseases, Recep Tayyip Erdoğan UniversitySchool of Medicine, Department of Chest Diseases, Recep Tayyip Erdoğan UniversitySchool of Medicine, Department of Radiology, Recep Tayyip Erdoğan UniversitySchool of Medicine, Department of Public Health, Recep Tayyip Erdoğan UniversitySchool of Medicine, Department of Chest Diseases, Recep Tayyip Erdoğan UniversityAbstract Background Alpha-1 antitrypsin deficiency (AATD) is associated with increased susceptibility to chronic obstructive pulmonary disease (COPD). AATD results from mutations in the SERPINA1 gene and over 500 rare mutations have been identified. Despite these findings and recommendations from major healthcare organizations, testing of COPD patients and their family members for AATD remains inadequate. Methods We examined genotypes and clinical characteristics of COPD patients (index cases; n = 14) treated at Recep Tayyip Erdoğan University Chest Diseases Department and their relatives (n = 17). Results When index cases were compared with screened relatives positive for AATD (n = 14), index cases were older and more predominantly male than screened relatives. Both groups had extensive smoking histories. All of the index cases and one of the screened relatives had been diagnosed with COPD. Clinical characterization of the COPD cases (14 index cases; 1 screened relative) showed that they had moderate to severe COPD with pre-treatment AAT levels of 0.59 ± 0.40 g/L (mean ± SD) and a COPD Assessment Test (CAT) score of 16.0 ± 8.12. The majority of these patients (73.3%) had panlobular emphysema. Five of the patients were treated with AAT augmentation which led to a decrease in the number of COPD exacerbations. Genotyping revealed that the most common rare allele identified in this population was MPalermo (c.227_229delTCT mutation on the M1(Val213) allelic background). Conclusions More testing and research need to be done to identify the relative prevalence of rare AATD variants. Earlier identification could lead to more effective treatment of affected individuals and improvement in their quality of life.https://doi.org/10.1186/s12890-024-03421-yAlpha-1 antitrypsin deficiencyMPalermoMMaltonCOPDScreeningTobacco
spellingShingle Dilek Karadoğan
Bettina Dreger
Lourdes Osaba
Enes Ahmetoğlu
Songül Özyurt
Bilge Yılmaz Kara
Nur Hürsoy
Tahsin Gökhan Telatar
Ünal Şahin
Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
BMC Pulmonary Medicine
Alpha-1 antitrypsin deficiency
MPalermo
MMalton
COPD
Screening
Tobacco
title Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
title_full Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
title_fullStr Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
title_full_unstemmed Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
title_short Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in Türkiye
title_sort clinical implications of the serpina1 variant mpalermo and alpha 1 antitrypsin deficiency in turkiye
topic Alpha-1 antitrypsin deficiency
MPalermo
MMalton
COPD
Screening
Tobacco
url https://doi.org/10.1186/s12890-024-03421-y
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