title: Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency.
abstract: BACKGROUND
  SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C.
  
  
  METHODS
  We have developed three quantitative PCR (QT-PCR) assays (1A, 1B and 1C). These assays were applied for the analysis of SERPINA1 alternative transcripts in: (1) 16 human tissues and (2) peripheral blood leukocytes from 33 subjects with AAT mutations and 7 controls.
  
  
  RESULTS
  Tissue-specific expression was found for the SERPINA1 transcripts. The 1A transcripts were mainly expressed in leukocytes and lung tissue while those detected with the 1B assay were highly restricted to leukocytes. Only 1B transcripts significantly correlated with serum AAT levels. The 1C transcripts were specifically found in lung, liver, kidney and pancreas. Furthermore, the expression of transcripts was related to AAT genotypes. While deficient variants of AAT had no pronounced effect on the transcript expression, null alleles were associated with significant reduction of different transcripts.
  
  
  CONCLUSIONS
  The possibility to discriminate between SERPINA1 alternative splicing products will help us to understand better the regulation of SERPINA1 gene and its association with SERPINA1 mutations-related diseases.
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. nmatamala@externos.isciii.es.
authors.forename: Nerea
authors.initials: N
authors.lastname: Matamala
authors.affiliation: Pneumology Department, Hospital 12 de Octubre, Madrid, Spain. mariateresa.martinez.martinez@salud.madrid.org.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Martínez
authors.affiliation: Respiratory Medicine Department, Royal Exeter and Devon Hospital, Exeter, Devon, UK. beat1135@gmail.com.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lara
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. lperezg@isciii.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. ivazquez@isciii.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Vázquez
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. azucenoide29@hotmail.com.
authors.forename: Azucena
authors.initials: A
authors.lastname: Jimenez
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. miguel_306_92@hotmail.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Barquín
authors.affiliation: Section of Pneumology, Department of Molecular Medicine, Center for Diagnosis of Inherited Alpha-1 Antitrypsin Deficiency, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy. I.Ferrarotti@smatteo.pv.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.affiliation: Alpha1-Antitrypsin Deficiency Spanish Registry, Lung Foundation RESPIRA, Spanish Society of Pneumology (SEPAR), Barcelona, Spain. ignablanco@yahoo.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Hanover, Germany. sabinajanciauskiene@gmail.com.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30626, Hanover, Germany. sabinajanciauskiene@gmail.com.
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km 2,200, 28220, Majadahonda, Madrid, Spain. bmartinezd@isciii.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martinez-Delgado
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin