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The prevalence of alpha-1 antitrypsin deficiency in Ireland

The prevalence of alpha-1 antitrypsin deficiency in Ireland
The prevalence of alpha-1 antitrypsin deficiency in Ireland
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
1465-9921
91-97
Carroll, T.P.
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O'Connor, C.A.
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Floyd, O.
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McPartlin, J.
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Kelleher, D.P.
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O'Brien, G.
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Dimitrov, B.D.
366d715f-ffd9-45a1-8415-65de5488472f
Morris, V.B.
f8a5802b-acb1-404c-82c0-0bc1fa6931ee
Taggart, C.C.
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McElvaney, N.G.
449577f3-4dd7-4a8d-a9a0-6c642c64233e
Carroll, T.P.
86fd7cb4-38f4-4b2b-89ce-cc380f05540e
O'Connor, C.A.
bcdf5012-2453-49b3-be66-aba2a13a086b
Floyd, O.
1c20508c-c4dd-4592-90ed-569892412ac6
McPartlin, J.
f95bad05-7ad1-4d45-9122-9647fa9740aa
Kelleher, D.P.
3d7146f6-9525-4894-96f5-509606b4fa02
O'Brien, G.
6d2ea79e-a265-4ad6-a5f7-3dce7a305d98
Dimitrov, B.D.
366d715f-ffd9-45a1-8415-65de5488472f
Morris, V.B.
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Taggart, C.C.
e54d1733-eaf6-43ea-a793-950e95062d28
McElvaney, N.G.
449577f3-4dd7-4a8d-a9a0-6c642c64233e

Carroll, T.P., O'Connor, C.A., Floyd, O., McPartlin, J., Kelleher, D.P., O'Brien, G., Dimitrov, B.D., Morris, V.B., Taggart, C.C. and McElvaney, N.G. (2011) The prevalence of alpha-1 antitrypsin deficiency in Ireland. Respiratory Research, 12 (1), 91-97. (doi:10.1186/1465-9921-12-91). (PMID:21752289)

Record type: Article

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

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e-pub ahead of print date: January 2011
Published date: 13 July 2011
Organisations: Primary Care & Population Sciences

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Local EPrints ID: 337419
URI: https://eprints.soton.ac.uk/id/eprint/337419
ISSN: 1465-9921
PURE UUID: 9b2efc17-9e42-416a-8c86-925862a832e9

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Date deposited: 26 Apr 2012 07:53
Last modified: 30 Jul 2019 18:57

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Contributors

Author: T.P. Carroll
Author: C.A. O'Connor
Author: O. Floyd
Author: J. McPartlin
Author: D.P. Kelleher
Author: G. O'Brien
Author: B.D. Dimitrov
Author: V.B. Morris
Author: C.C. Taggart
Author: N.G. McElvaney

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