title: The prevalence of alpha-1 antitrypsin deficiency in Ireland.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. tcarroll@rcsi.ie
authors.forename: Tomás P
authors.initials: TP
authors.lastname: Carroll
authors.forename: Catherine A
authors.initials: CA
authors.lastname: O'Connor
authors.forename: Olwen
authors.initials: O
authors.lastname: Floyd
authors.forename: Joseph
authors.initials: J
authors.lastname: McPartlin
authors.forename: Dermot P
authors.initials: DP
authors.lastname: Kelleher
authors.forename: Geraldine
authors.initials: G
authors.lastname: O'Brien
authors.forename: Borislav D
authors.initials: BD
authors.lastname: Dimitrov
authors.forename: Valerie B
authors.initials: VB
authors.lastname: Morris
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Taggart
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
mesh_terms: D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006306:Health Surveys; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008403:Mass Screening / Q000379:methods; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D000515:alpha 1-Antitrypsin / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin