SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations.
BACKGROUND
Individuals with severe deficiency in serum alpha(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 < or = 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 < or = 1.13 and from > 0.93 to < or = 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 < or = 0.83 g/L.


CONCLUSIONS
This analysis provided a detailed molecular definition of intermediate AATD, which would be helpful in the diagnostic setting.
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.
Michele
M
Zorzetto
Erich
E
Russi
Oliver
O
Senn
Medea
M
Imboden
Ilaria
I
Ferrarotti
Carmine
C
Tinelli
Ilaria
I
Campo
Stefania
S
Ottaviani
Roberta
R
Scabini
Arnold
A
von Eckardstein
Wolfgang
W
Berger
Otto
O
Brändli
Thierry
T
Rochat
Maurizio
M
Luisetti
Nicole
N
Probst-Hensch
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000097:blood*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin