Rare A1AT variants in Polish patients with chronic respiratory disorders – Data from 2013 to 2016

SERPINA1 gene encoding the alpha-1 antitrypsin (A1AT) protein is highly polymorphic. Apart from the most prevalent PI*S and PI*Z deficiency alleles, other so-called rare variants also predispose individuals to severe chronic respiratory disorders (CRDs). Our aim was to assess the frequency of common and rare SERPINA1 mutations in a group of 1749 Polish patients with CRDs referred for A1AT deficiency diagnosticsbetween 2013-2016. A1AT concentration was assessed by nephelometry, phenotype by isoelectric focusing followed by PCR genotyping and/or direct sequencing. Further on, samples from 100 consecutive patients with an A1AT concentration 85.5% samples carried the normal PI*MM genotype, whereas in 14.5%, at least one A1AT deficiency variant was detected. PI*S (1.9%) and PI*Z (11.9%) alleles were identified yielding frequencies of 0.011 and 0.069, respectively. Rare A1AT variants were detected in 11 patients: PI*F (n=5) and PI*I (n=5). Also PI*M6 Passau and c.573delG indicating heterozygous Null variant were revealed in 1 patient. Retrospective analysis of SERPINA1 gene by direct sequencing in 100 patients revealed rare A1AT alleles: PI*M2 Obernburg (n=1), c.922Gu003eT (n=1), PI*P Lowell (n=1) and PI*M wurzburg (n=1). No PI*M malton allele was detected. The prevalence of the PI*F and PI*I alleles in Polish CRD patients seems higher than in others European studies. PI*Mmalton, the most prevalent rare variant in Southern Europe, was not detected. Common PI*Z A1AT deficiency allele is considerably more common in CRDs subjects than in general Polish population.