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Alpha-1-antitrypsin deficiency
Original article
Serum levels and genotype distribution of α1-antitrypsin in the general population
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  1. Ilaria Ferrarotti1,
  2. Gian Andri Thun2,3,
  3. Michele Zorzetto1,
  4. Stefania Ottaviani1,
  5. Medea Imboden2,3,
  6. Christian Schindler2,3,
  7. Arnold von Eckardstein4,
  8. Lucia Rohrer4,
  9. Thierry Rochat5,
  10. Erich W Russi6,
  11. Nicole M Probst-Hensch2,3,
  12. Maurizio Luisetti1
  1. 1Center for Diagnosis of Inherited Alpha1-antitrypsin Deficiency, Department of Molecular Medicine, Section of Pneumology, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
  2. 2Unit Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland
  3. 3University of Basel, Basel, Switzerland
  4. 4Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland
  5. 5Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland
  6. 6Division of Pulmonary Medicine, University Hospital of Zürich, Zürich, Switzerland
  1. Correspondence to Dr Maurizio Luisetti, IRCCS San Matteo Hospital Foundation, University of Pavia, Piazza Golgi 1, 27100 Pavia, Italy; m.luisetti{at}smatteo.pv.it

Abstract

Rationale α1-Antitrypsin (AAT) deficiency is one of the commonest rare respiratory disorders worldwide. Diagnosis, assessment of risk for developing chronic obstructive pulmonary disease (COPD), and management of replacement therapy require the availability of precise and updated ranges for protein serum levels.

Objective This paper aims to provide ranges of serum AAT according to the main genotype classes in the general population.

Methods The authors correlated mean AAT serum levels with the main SERPINA1 variants (M1Ala/M1Val (rs6647), M3 (rs1303), M2/M4 (rs709932), S (rs17580) and Z (rs28929474)) in 6057 individuals enrolled in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) cohort.

Results The following ranges (5th–95th percentile) of AAT were found in the serum (g/litre): 1.050–1.640 for PI*MM, 0.880–1.369 for PI*MS, 0.730–1.060 for PI*SS, 0.660–0.997 for PI*MZ and 0.490–0.660 for PI*SZ. There was very little overlap in AAT serum levels between genotype classes generally not believed to confer an enhanced health risk (MM and MS) and those associated with an intermediate AAT deficiency and a potentially mildly enhanced health risk (SS, MZ).

Conclusion This work resulted in three important findings: technically updated and narrower serum ranges for AAT according to PI genotype; a suggestion for a population-based ‘protective threshold’ of AAT serum level, used in decision-making for replacement therapy; and more precise ranges framing the intermediate AAT deficiency area, a potential target for future primary prevention.

  • Pulmonary emphysema
  • chronic liver disease
  • genetic risk factors
  • serpin A1
  • α1-antitrypsin deficiency
  • lung proteases
  • rare lung diseases
  • COPD epidemiology
  • oxidative stress
  • interstitial fibrosis
  • non-small cell lung cancer
  • rare lung diseases
  • COPD mechanisms
  • COPD epidemiology
  • COPD exacerbations
  • lung transplantation
  • tuberculosis

https://doi.org/10.1136/thoraxjnl-2011-201321

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    Footnotes

    • Funding Unrestricted grant to IF and G-AT and eALTA 2006 assigned to IF, both provided by Talecris Biotherapeutics Inc.; funds from the Fondazione IRCCS Policlinico San Matteo—Ricerca Corrente (RC345) and from the Fondazione Cariplo. Support to SAPALDIA: The Swiss National Science Foundation (grants 33CS30_134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, 3233-054996, PDFMP3-123171), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Zurich, the Swiss Lung League, the canton's Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticino and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA.

    • Competing interests IF has received educational and consultancy fees, a research grant (eALTA Award) and an urestricted grant, and travel support from Talecris Biotherapeutics GmbH and Kedrion SpA. Part of the salary costs of GAT are covered by an unrestricted research grant from TalecrisBiotherapeutics GmbH. TR has received fees for consulting once in 2011 by Talecris Biotherapeutics GmbH. SO has received travel support from Grifols International SA and consultancy fees from Kedrion SpA. ML has received travel costs to ERS and ATS congresses from Talecris Biotherapeutics GmbH, he has performed paid lectures for Kedrion SpA, and has obtained research funds from Talecris Biotherapeutics GmbH, as well as funds for staff members. NPH has received an unrestricted research grant from Talecris GmbH. The grant money was applied to covering part of the salary costs for GAT. The company was not involved in defining specific aims, conduct of data analysis or data interpretation. All other authors declare no conflict of interest.

    • Patient consent Obtained.

    • Ethics approval Swiss Academy of Medical Science and Cantonal Ethics Committees for each of the eight examination areas.

    • Provenance and peer review Not commissioned; externally peer reviewed.