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This Article Full Text Full Text (PDF) Supplement Data All Versions of this Article: clinchem.2007.102798v1 54/8/1331    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Zorzetto, M. Search for Related Content PubMed PubMed Citation Articles by Zorzetto, M. Related Collections Molecular Diagnostics and Genetics

SERPINA1 Gene Variants in Individuals from the General Population with Reduced ₁-Antitrypsin Concentrations

¹ Center for Diagnosis of Severe Alpha1-antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease and Unit of Statistics and Biometry, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy; ² Pulmonary Division, University Hospital of Zurich, Switzerland; ³ Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine and Clinical Pathology, University of Zurich, Switzerland; ⁴ Institute of Clinical Chemistry, University Hospital of Zürich, Switzerland;⁵ Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Switzerland; ⁶ Zürcher Höhenklinik Wald, Switzerland; ⁷ Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland.

^aAddress correspondence to this author at: University Hospital Zürich, Vogelsangstr. 10, 8091 Zürich, Switzerland. Fax 0041-44-255-56-36; e-mail Nicole.Probst{at}usz.ch.

Background: Individuals with severe deficiency in serum ₁-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 25 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.

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				M. R. Snyder and W. E. Highsmith Jr Commentary Clin. Chem., August 1, 2008; 54(8): 1399 - 1399. [Full Text] [PDF]