The prevalence of alpha-1 antitrypsin deficiency in Ireland.

Hdl Handle:
http://hdl.handle.net/10147/207049
Title:
The prevalence of alpha-1 antitrypsin deficiency in Ireland.
Authors:
Carroll, Tomas P; O'Connor, Catherine A; Floyd, Olwen; McPartlin, Joseph; Kelleher, Dermot P; O'Brien, Geraldine; Dimitrov, Borislav D; Morris, Valerie B; Taggart, Clifford C; McElvaney, Noel G
Affiliation:
Department of Medicine, Royal College of Surgeons in Ireland Education and, Research Centre, Beaumont Hospital, Dublin 9, Ireland. tcarroll@rcsi.ie
Citation:
Respir Res. 2011 Jul 13;12:91.
Journal:
Respiratory research
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207049
DOI:
10.1186/1465-9921-12-91
PubMed ID:
21752289
Abstract:
BACKGROUND: 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.
Language:
eng
MeSH:
Chi-Square Distribution; DNA Mutational Analysis; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Health Surveys; Humans; Ireland/epidemiology; Mass Screening/methods; Mutation; Odds Ratio; Phenotype; Prevalence; Risk Assessment; Risk Factors; alpha 1-Antitrypsin/genetics; alpha 1-Antitrypsin Deficiency/diagnosis/*epidemiology/genetics
ISSN:
1465-993X (Electronic); 1465-9921 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorCarroll, Tomas Pen_GB
dc.contributor.authorO'Connor, Catherine Aen_GB
dc.contributor.authorFloyd, Olwenen_GB
dc.contributor.authorMcPartlin, Josephen_GB
dc.contributor.authorKelleher, Dermot Pen_GB
dc.contributor.authorO'Brien, Geraldineen_GB
dc.contributor.authorDimitrov, Borislav Den_GB
dc.contributor.authorMorris, Valerie Ben_GB
dc.contributor.authorTaggart, Clifford Cen_GB
dc.contributor.authorMcElvaney, Noel Gen_GB
dc.date.accessioned2012-02-01T09:58:02Z-
dc.date.available2012-02-01T09:58:02Z-
dc.date.issued2012-02-01T09:58:02Z-
dc.identifier.citationRespir Res. 2011 Jul 13;12:91.en_GB
dc.identifier.issn1465-993X (Electronic)en_GB
dc.identifier.issn1465-9921 (Linking)en_GB
dc.identifier.pmid21752289en_GB
dc.identifier.doi10.1186/1465-9921-12-91en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207049-
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_GB
dc.language.isoengen_GB
dc.subject.meshChi-Square Distributionen_GB
dc.subject.meshDNA Mutational Analysisen_GB
dc.subject.meshGene Frequencyen_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshGenetic Testingen_GB
dc.subject.meshHealth Surveysen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIreland/epidemiologyen_GB
dc.subject.meshMass Screening/methodsen_GB
dc.subject.meshMutationen_GB
dc.subject.meshOdds Ratioen_GB
dc.subject.meshPhenotypeen_GB
dc.subject.meshPrevalenceen_GB
dc.subject.meshRisk Assessmenten_GB
dc.subject.meshRisk Factorsen_GB
dc.subject.meshalpha 1-Antitrypsin/geneticsen_GB
dc.subject.meshalpha 1-Antitrypsin Deficiency/diagnosis/*epidemiology/geneticsen_GB
dc.titleThe prevalence of alpha-1 antitrypsin deficiency in Ireland.en_GB
dc.contributor.departmentDepartment of Medicine, Royal College of Surgeons in Ireland Education and, Research Centre, Beaumont Hospital, Dublin 9, Ireland. tcarroll@rcsi.ieen_GB
dc.identifier.journalRespiratory researchen_GB
dc.description.provinceLeinster-

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