title: Rare alpha-1-antitrypsin variants: are they really so rare?
abstract: Alpha-1-antitrypsin (α1-AT) deficiency is mainly evaluated in the diagnostic process of chronic obstructive pulmonary disease (COPD). Around 95% of individuals with severe α1-AT deficiency carry the PI*ZZ genotype. Little is known about the epidemiology of the remaining deficient α1-AT variants, which are called 'rare' due to their low prevalence. The retrospective revision of 3511 α1-AT deficiency determinations performed in Barcelona from 1998 to 2010 detected 1.6% of cases with rare α1-AT alleles, a rate similar to those reported in other European studies. Among these variants, PI*I and PI*Mmalton represented 54% of cases. Hence, the so-called 'rare' α1-AT alleles may not be rare as has been assumed. It would be of interest to implement simple allele-specific molecular biology methods to study the most prevalent rare variants in each region. Augmentation therapy is recommended in patients with emphysema and PI*ZZ genotype, but there is little evidence regarding the implications of rare variants on therapy.
authors.affiliation: Servicio de Bioquímica, Hospital Universitario Vall d’Hebrón, Paseo Valle Hebrón s/n, Barcelona 08035, Spain. frarodri@vhebron.net
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Frias
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
authors.forename: Rafael
authors.initials: R
authors.lastname: Vidal
authors.forename: Silvia
authors.initials: S
authors.lastname: Camos
authors.forename: Rosendo
authors.initials: R
authors.lastname: Jardi
mesh_terms: D000483:Alleles; D005838:Genotype; D006801:Humans; D012189:Retrospective Studies; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics
chemical_list: D000515:alpha 1-Antitrypsin