TY - JOUR
T1 - SERPINA1 gene variants in individuals from the general population with reduced α1-antitrypsin concentrations
AU - Zorzetto, Michele
AU - Russi, Erich
AU - Senn, Oliver
AU - Imboden, Medea
AU - Ferrarotti, Ilaria
AU - Tinelli, Carmine
AU - Campo, Ilaria
AU - Ottaviani, Stefania
AU - Scabini, Roberta
AU - Von Eckardstein, Arnold
AU - Berger, Wolfgang
AU - Brändli, Otto
AU - Rochat, Thierry
AU - Luisetti, Maurizio
AU - Probst-Hensch, Nicole
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
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U2 - 10.1373/clinchem.2007.102798
DO - 10.1373/clinchem.2007.102798
M3 - Article
C2 - 18515255
AN - SCOPUS:48949095935
VL - 54
SP - 1331
EP - 1338
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 8
ER -