title: Frequency of Rare Alpha-1 Antitrypsin Variants in Polish Patients with Chronic Respiratory Disorders.
abstract: The SERPINA1 gene encoding the alpha-1 antitrypsin (A1AT) protein is highly polymorphic. It is known that, apart from the most prevalent PI*S and PI*Z A1AT deficiency variants, other so-called rare variants also predispose individuals to severe chronic respiratory disorders such as emphysema and chronic obstructive pulmonary disease. Our aim was to assess the frequencies of common and rare SERPINA1 mutations in a group of 1033 Polish patients referred for A1AT deficiency diagnostics due to chronic respiratory disorders in the period of January 2014-September 2015. All blood samples were analyzed according to the routine diagnostic protocol, including A1AT serum concentration assessment by nephelometry and immune isoelectric focusing, followed by PCR genotyping and direct sequencing when necessary. A total of 890 out of the 1033 samples (86 %) carried the normal PI*MM genotype, whereas, in 143 samples (14 %), at least one A1AT deficiency variant was detected. In 132 subjects, PI*S (2.1 %) and PI*Z (10.8 %) common deficiency alleles were identified, yielding frequencies of 0.011 and 0.062, respectively. Rare SERPINA1 variants were detected in nine patients: PI*F (c.739C>T) (n = 5) and PI*I (c.187C>T) (n = 4). Samples from the patients with an A1AT serum concentration below 120 mg/dl and presenting a PI*MM-like phenotypic pattern were retrospectively analyzed by direct sequencing for rare SERPINA1 mutations, revealing a PI*M2Obernburg (c.514G>T) mutation in one patient and a non-pathogenic mutation (c.922G>T) in another. We conclude that the deficiency PI*Z A1AT allele is considerably more common in patients with chronic respiratory disorders than in the general Polish population. The prevalence of the PI*F allele seems higher than in other European studies.
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Płocka St., 01-138, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Duk
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Płocka St., 01-138, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Zdral
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Płocka St., 01-138, Warsaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Szumna
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Płocka St., 01-138, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Roży
authors.affiliation: Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Płocka St., 01-138, Warsaw, Poland. j.chorostowska@igichp.edu.pl.
authors.forename: J
authors.initials: J
authors.lastname: Chorostowska-Wynimko
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D014890:Granulomatosis with Polyangiitis / Q000235:genetics*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics; D011656:Pulmonary Emphysema / Q000235:genetics*; D044465:White People / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin
keywords: Alpha-1 antitrypsin; Antitrypsin variants; Diagnosis of deficiency; Hereditary disorders; SERPINA1