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dc.contributor.authorKELLEHER, DERMOTen
dc.contributor.authorMCPARTLIN, JOSEPHen
dc.date.accessioned2011-09-07T11:54:45Z
dc.date.available2011-09-07T11:54:45Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationCarroll, TP, O'Connor, CA, Floyd, O, McPartlin, J, Kelleher, DP, O'Brien, G, Dimitrov, BD, Morris, VB, Taggart, CC, McElvaney, NG, The prevalence of alpha-1 antitrypsin deficiency in Ireland, RESPIRATORY RESEARCH, 12, 91, 2011en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/59332
dc.descriptionPUBLISHEDen
dc.description.abstractBackground: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. Methods: We present data from the first 3,000 individuals screened following ATS/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. Results: The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. Conclusion: Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.en
dc.description.sponsorshipThis work has been supported by funding from the Irish Government Department of Health and Children, Alpha One Foundation (Ireland), Alpha-1 Foundation (USA), Health Research Board (HRB) and Medical Research Charities Group (MRCG), and the Programme for Research in Third Level Institutes (PRTLI). The authors wish to thank Larry Warren, former CEO of the Alpha One Foundation (Ireland), Pat O'Brien and Eric Mahon in the Biochemistry Department, Beaumont Hospital for vital help with patient sampling and electrophoresis techniques, Professor Maurizio Luisetti and Dr. Ilaria Ferrarotti at the University of Pavia in Italy for sequencing of rare SERPINA1 mutations, and John Walsh and Angela McBride of the Alpha-1 Foundation (USA). We would also like to acknowledge the contribution of the following hospitals; Bon Secours Hospital Tralee, Bon Secours Hospital Dublin, Cavan General Hospital, Cork University Hospital, James Connolly Memorial Hospital Blanchardstown, Letterkenny General Hospital, Limerick Regional Hospital, Mayo General Hospital, Mercy University Hospital Cork, Mullingar Regional Hospital, Our Lady of Lourdes Hospital Drogheda, Peamount Hospital Dublin, Sligo General Hospital, St James's Hospital Dublin, St. Vincent's University Hospital Dublin, The Adelaide and Meath Hospitals including National Children's Hospital Tallaght, The Mater Misericordiae University Hospital Dublin, and Waterford Regional Hospital.en
dc.language.isoenen
dc.relation.ispartofseriesRESPIRATORY RESEARCHen
dc.relation.ispartofseries12en
dc.relation.ispartofseries91en
dc.rightsYen
dc.subjectEndocrinology and metabolismen
dc.subjectGeneticsen
dc.subjectemphysemaen
dc.subjectliver diseaseen
dc.subjectIrelanden
dc.titleThe prevalence of alpha-1 antitrypsin deficiency in Irelanden
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kellehdpen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/jmcprtlnen
dc.identifier.rssinternalid74867en
dc.subject.TCDThemeCanceren
dc.subject.TCDThemeGenes & Societyen
dc.identifier.rssurihttp://dx.doi.org/10.1186/1465-9921-12-91en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.contributor.sponsorHigher Education Authority (HEA)en


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