Chest
Original ResearchCOPDα1-Antitrypsin Phenotypes and Associated Serum Protein Concentrations in a Large Clinical Population
Section snippets
Materials and Methods
A retrospective database was generated consisting of patient age in years, sex, patient race (when available), reported AAT phenotypes, and measured AAT concentrations for patient serum samples consecutively submitted for AAT phenotyping by IEF electrophoresis and concurrent AAT serum concentration determination to ARUP Laboratories. All samples were treated in accordance with procedures approved by the institutional review board of the University of Utah (IRB 7275).
Pi protein phenotypes were
Results
The observed protein phenotypes and associated serum concentrations are summarized in Table 1. A total of 1,664 patient samples had two apparent deficiency phenotype alleles and were classified as at-risk phenotypes. Of these, 99 samples contained a rare deficiency allele paired with an S or Z deficiency allele, and nine samples harbored two rare deficiency alleles (Pi FF, PP, II, TT). Three Null phenotype samples exhibiting no apparent AAT variant were classified at risk. Additionally, 16,893
Discussion
The large number of native PiMM individuals in this study allowed for investigation of differences in normal populations.35 As expected, the M1, M2, and M3 variants had no significant effect on serum AAT concentrations.11 Median AAT concentrations were slightly lower in males (P ≤ .01), although the magnitude of this effect is likely not clinically significant. Interestingly, PiMM individuals broadly designated as Asian exhibited significantly (P ≤ .05) lower AAT concentrations when compared
Acknowledgments
Author contributions: Dr Bornhorst had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Dr Bornhorst: contributed to the study design, data collection, data analyses, and manuscript writing.
Dr Greene: contributed to the study design, data analyses, and manuscript writing.
Dr Ashwood: contributed to the study design, data collection, data analyses, and manuscript writing.
Dr Grenache: contributed to the study
References (50)
The alpha 1-antitrypsin gene and its deficiency states
Trends Genet
(1989)- et al.
Detection of alpha-1 antitrypsin deficiency: a review
Respir Med
(2009) - et al.
Alpha1-antitrypsin deficiency
Lancet
(2005) - et al.
Smoking, lung function, and alpha 1-antitrypsin deficiency
Lancet
(1985) - et al.
Alpha 1-antitrypsin PiM subtypes and chronic obstructive pulmonary disease (COPD)
Chest
(1982) - et al.
Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem
Chest
(2005) - et al.
Impact of a clinical decision support system in an electronic health record to enhance detection of α1-antitrypsin deficiency
Chest
(2011) - et al.
Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program
Respir Med
(2007) - et al.
Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003
Chest
(2005) - et al.
Isoelectric focusing in immobilized pH gradients: applications in clinical chemistry and forensic analysis
J Chromatogr A
(1991)
Diagnostic flow chart for targeted detection of alpha1-antitrypsin deficiency
Respir Med
AAT as a diagnostic tool
Clin Chim Acta
Kinetic characterisation of alpha-1-antitrypsin F as an inhibitor of human neutrophil elastase
Pathology
The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy
Chest
Acute phase reactants in the elderly
Clin Chim Acta
Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes
Chest
Alpha 1-antitrypsin deficiency. 3: clinical manifestations and natural history
Thorax
Liver disease in alpha 1-antitrypsin deficiency: a review
Am J Gastroenterol
Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed
Environ Health Perspect
Genetic epidemiology of alpha-1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America
Clin Genet
Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency
Thorax
Alpha-1-antitrypsin deficiency. High prevalence in the St. Louis area determined by direct population screening
Am Rev Respir Dis
Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk
Thorax
A review of α1-antitrypsin deficiency
Am J Respir Crit Care Med
Clinical features of individuals with PI*SZ phenotype of alpha 1-antitrypsin deficiency. alpha 1-Antitrypsin Deficiency Registry Study Group
Am J Respir Crit Care Med
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Funding/Support: This work was supported by the ARUP Institute for Clinical and Experimental Pathology.
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