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Respiration. 2011;82(5):418-25. doi: 10.1159/000325067. Epub 2011 Apr 6.

Population genetic screening for alpha1-antitrypsin deficiency in a high-prevalence area.

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Centro di Riferimento Regionale per il Deficit di Alfa1-Antitripsina, Prima Divisione di Medicina Interna, Spedali Civili, Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, Brescia, Italy.



Current guidelines for α1-antitrypsin deficiency (AATD) state that adult population screening should only be done in high-risk areas. Up-to-date genetic methods are always recommended.


To determine the prevalence of AATD in a suspected high-risk area by population screening, applying new genetic analyses and comparing the prevalence of liver and lung abnormalities in subjects with or without AATD.


Adult residents of Pezzaze, a village in an Italian alpine valley, voluntarily participated in the screening, and were examined for: nephelometric α1-antitrypsin (AAT) serum level, DNA analysis (mutagenic polymerase chain reaction and restriction fragment length polymorphism tests for Z and S AATD causative mutations, and denaturing high-performance liquid chromatography and/or direct gene sequencing if needed), serum aspartate and alanine transaminases, a respiratory questionnaire and the Medical Research Council dyspnea index scale. The prevalence of AATD was compared with that expected in Italy (Hardy-Weinberg equilibrium), and transaminases and the prevalence of respiratory symptoms were compared between study groups.


Of 1,353 residents, 817 (60.4%) participated; 67 (8.2%) had low AAT serum levels (<90 mg/dl); 118 were carriers of AATD-associated alleles, 4 (0.5%) homozygotes or compound heterozygotes (1 Z, 1 S, 2 ZP(brescia)), 114 (14%) heterozygotes (46 Z, 52 S, 9 P(brescia), 4 M(wurzburg), 2 I, 1 P(lowell)). The prevalence and frequency of all AATD-related alleles was higher than expected for Italy (p < 0.001). There were no differences in symptoms of respiratory disease and transaminases between individuals with normal and low serum AAT.


The screening design is one of the main strengths of this study. The large number of mostly asymptomatic individuals with AATD identified suggests that in high-risk areas adult population screening programs employing the latest genetic methods are feasible. Early recognition of individuals at risk means primary or secondary prevention measures can be taken.

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