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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.

Author information

1
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. luciano.corda@spedalicivili.brescia.it

Abstract

BACKGROUND:

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.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
21474916
DOI:
10.1159/000325067
[Indexed for MEDLINE]
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