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dc.contributor.authorMatamala, Nerea 
dc.contributor.authorVarela Martinez, Maria del Carmen 
dc.contributor.authorLara, Beatriz
dc.contributor.authorPerez, Laura 
dc.contributor.authorVazquez-Dominguez, Irene 
dc.contributor.authorJimenez, Azucena
dc.contributor.authorBarquín, Miguel
dc.contributor.authorFerrarotti, Ilaria
dc.contributor.authorBlanco, Ignacio
dc.contributor.authorJanciauskiene, Sabina
dc.contributor.authorMartinez-Delgado, Beatriz
dc.identifier.citationJ Transl Med. 2015 Jul 4;13:211.es_ES
dc.description.abstractBACKGROUND: 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.es_ES
dc.description.sponsorshipWe thank collaborators from the REDAAT (Spanish Registry of Alpha-1 Antitrypsin deficiency patients) and all members of the Human Genetics Area of the ISCIII for their support. Special thanks to Prof. Halpin for reviewing the manuscript. This work has been partially funded by the Instituto de Salud Carlos III Grants TPY1250/12, TPY1269/15 and PI14CIII/00070 (BMD).es_ES
dc.publisherBioMed Central (BMC) es_ES
dc.subject.meshAlleles es_ES
dc.subject.meshAlternative Splicing es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLeukocytes es_ES
dc.subject.meshMutation es_ES
dc.subject.meshOrgan Specificity es_ES
dc.subject.meshProtein Isoforms es_ES
dc.subject.meshRNA, Messenger es_ES
dc.subject.meshReal-Time Polymerase Chain Reaction es_ES
dc.subject.meshTranscription, Genetic es_ES
dc.subject.meshalpha 1-Antitrypsin es_ES
dc.subject.meshalpha 1-Antitrypsin Deficiency es_ES
dc.titleAlternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiencyes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.identifier.journalJournal of translational medicinees_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.rights.accessRightsopen accesses_ES

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