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. 2011 Jul 13;12(1):91.
doi: 10.1186/1465-9921-12-91.

The prevalence of alpha-1 antitrypsin deficiency in Ireland

Tomás P Carroll  1 , Catherine A O'Connor, Olwen Floyd, Joseph McPartlin, Dermot P Kelleher, Geraldine O'Brien, Borislav D Dimitrov, Valerie B Morris, Clifford C Taggart, Noel G McElvaney
Affiliations

The prevalence of alpha-1 antitrypsin deficiency in Ireland

Tomás P Carroll et al. Respir Res. .

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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Figures

Figure 1
Figure 1
Percentage distribution of 3,000 INTDP patients according to reason for screening.
Figure 2
Figure 2
Methods employed for analysis of AAT mutations. (A) Typical isoelectric focusing gel used for identification of AAT phenotype. (B) Genotyping assay used to identify the Z mutation.
Figure 3
Figure 3
Analysis of AAT mutations in Ireland. (A) 1,100 DNA samples in the Biobank collection were genotyped for the S and Z mutations. (B) 3,000 Irish individuals were screened as part of the national targeted detection programme following ATS/ERS guidelines.
Figure 4
Figure 4
Comparison of S and Z allele frequencies in the Biobank population and in the INTDP population.
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References

    1. Laurell CB, Eriksson SE. The electrophoretic alpha-globulin pattern of serum in alpha1-antitrypsin deficiency. Scand J Clin Lab Invest. 1963;15:132–140.
    1. Sveger T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med. 1976;294:1316–1321. - PubMed
    1. Edmonds BK, Hodge JA, Rietschel RL. Alpha 1-antitrypsin deficiency-associated panniculitis: case report and review of the literature. Pediatr Dermatol. 1991;8:296–299. - PubMed
    1. King MA, Stone JA, Diaz PT, Mueller CF, Becker WJ, Gadek JE. Alpha 1-antitrypsin deficiency: evaluation of bronchiectasis with CT. Radiology. 1996;199:137–141. - PubMed
    1. Lewis M, Kallenbach J, Zaltzman M, Levy H, Lurie D, Baynes R, King P, Meyers A. Severe deficiency of alpha 1-antitrypsin associated with cutaneous vasculitis, rapidly progressive glomerulonephritis, and colitis. Am J Med. 1985;79:489–494. - PubMed

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