SERPINA1 gene variants in individuals from the general population with reduced α1-antitrypsin concentrations

Michele Zorzetto, Erich Russi, Oliver Senn, Medea Imboden, Ilaria Ferrarotti, Carmine Tinelli, Ilaria Campo, Stefania Ottaviani, Roberta Scabini, Arnold Von Eckardstein, Wolfgang Berger, Otto Brändli, Thierry Rochat, Maurizio Luisetti, Nicole Probst-Hensch

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Abstract

BACKGROUND: Individuals with severe deficiency in serum α1-antitrypsin (AAT) concentrations are at high risk for developing chronic obstructive pulmonary disease (COPD), whereas those carrying the PI*MZ genotype are at slightly increased risk. Testing appropriate subgroups of the population for AAT deficiency (AATD) is therefore an important aspect of COPD prevention and timely treatment. We decided to perform an exhaustive investigation of SERPINA1 gene variants in individuals from the general population with a moderately reduced serum AAT concentration, because such information is currently unavailable. METHODS: We determined the Z and S alleles of 1399 individuals enrolled in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) with serum AAT concentrations ≤1.13 g/L and submitted 423 of these samples for complete exon 2→5 sequencing. RESULTS: We found that 900 of 1399 samples (64%), carried the normal PI*MM genotype, whereas 499 samples (36%) carried at least 1 SERPINA1 deficiency variant. In the subpopulations in which AAT concentrations ranged from >1.03 to ≤1.13 and from >0.93 to ≤1.03 g/L, individuals with the PI*MM genotype represented the majority (86.5% and 53.8%, respectively). The PI*MS genotype was predominant (54.9%) in the AAT range of 0.83 to 0.93 g/L, whereas PI*MZ represented 76.4% in the AAT range of >0.73 to ≤0.83 g/L. CONCLUSIONS: This analysis provided a detailed molecular definition of intermediate AATD, which would be helpful in the diagnostic setting.

Original languageEnglish
Pages (from-to)1331-1338
Number of pages8
JournalClinical Chemistry
Volume54
Issue number8
DOIs
Publication statusPublished - Aug 1 2008

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ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Zorzetto, M., Russi, E., Senn, O., Imboden, M., Ferrarotti, I., Tinelli, C., Campo, I., Ottaviani, S., Scabini, R., Von Eckardstein, A., Berger, W., Brändli, O., Rochat, T., Luisetti, M., & Probst-Hensch, N. (2008). SERPINA1 gene variants in individuals from the general population with reduced α1-antitrypsin concentrations. Clinical Chemistry, 54(8), 1331-1338. https://doi.org/10.1373/clinchem.2007.102798