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.
| Original language | English |
|---|---|
| Pages (from-to) | 669-674 |
| Number of pages | 6 |
| Journal | Thorax |
| Volume | 67 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
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Serum levels and genotype distribution of α1-antitrypsin in the general population. / Ferrarotti, Ilaria; Thun, Gian Andri; Zorzetto, Michele; Ottaviani, Stefania; Imboden, Medea; Schindler, Christian; Von Eckardstein, Arnold; Rohrer, Lucia; Rochat, Thierry; Russi, Erich W.; Probst-Hensch, Nicole M.; Luisetti, Maurizio.
In: Thorax, Vol. 67, No. 8, 08.2012, p. 669-674.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum levels and genotype distribution of α1-antitrypsin in the general population
AU - Ferrarotti, Ilaria
AU - Thun, Gian Andri
AU - Zorzetto, Michele
AU - Ottaviani, Stefania
AU - Imboden, Medea
AU - Schindler, Christian
AU - Von Eckardstein, Arnold
AU - Rohrer, Lucia
AU - Rochat, Thierry
AU - Russi, Erich W.
AU - Probst-Hensch, Nicole M.
AU - Luisetti, Maurizio
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864018755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864018755&partnerID=8YFLogxK
U2 - 10.1136/thoraxjnl-2011-201321
DO - 10.1136/thoraxjnl-2011-201321
M3 - Article
C2 - 22426792
AN - SCOPUS:84864018755
VL - 67
SP - 669
EP - 674
JO - Thorax
JF - Thorax
SN - 0040-6376
IS - 8
ER -