title: Incidence of alpha-1 antitrypsin Z and S alleles in patients with granulomatosis with polyangiitis--pilot study.
abstract: BACKGROUND
  Inherited alpha-1 antitrypsin (AAT) deficiency is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. It has also been suggested that AAT deficiency might be instrumental vasculitis associated with the anti-neutrophil cytoplasm antibodies (cANCA) and subsequent lung tissue injury.
  
  
  METHODS
  We present the results from a pilot study involving 51 patients with granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis (GPA), 43 of whom were cANCA positive. The control group consisted of 658 individuals. AAT blood concentration assessment by nephelometry, phenotyping by isoelectrofocusing and real-time PCR genotyping were performed.
  
  
  RESULTS
  Deficiency alleles PI*Z and PI*S were detected in 3 (5.88%) and in 2 patients (3.92%) with GPA, respectively. All of them were cANCA positive. In the controls, PI*Z was observed in 2.8% while PI*S in 1.5% of cases. Accordingly, the increased incidence of main deficiency alleles was demonstrated in GPA, and particularly in cANCA+GPA patients, when compared to the controls. The estimated frequency for PI*Z in GPA, cANCA+GPA patients and controls was, respectively, 29.4/1000, 34.9/1000 and 13.7/1000, whereas for PI*S it was 19.2/1000, 23.2/10,00 and 7.6/1000. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. CONSCLUSIONS: We believe that our preliminary data confirm the clinical importance of AAT deficiency in GPA patients and the need to screen for AAT deficiency alleles. The study is on-going.
authors.affiliation: Laboratory of Molecular Diagnostics and Immunology , National Institute of Tuberculosis and Lung Diseases, Warsaw. immuno@igichp.edu.pl
authors.forename: Joanna
authors.initials: J
authors.lastname: Chorostowska-Wynimko
authors.forename: Dariusz
authors.initials: D
authors.lastname: Gawryluk
authors.forename: Radosław
authors.initials: R
authors.lastname: Struniawski
authors.forename: Beata
authors.initials: B
authors.lastname: Popławska
authors.forename: Justyna
authors.initials: J
authors.lastname: Fijołek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011044:Poland / Q000453:epidemiology; D015995:Prevalence; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000515:alpha 1-Antitrypsin