title: Genotyping increases the yield of angiotensin-converting enzyme in sarcoidosis--a systematic review.
abstract: BACKGROUND
  The diagnosis of sarcoidosis is challenging and involves radiological, clinical and paraclinical evaluation, the latter including the measurement of serum angiotensin-converting enzyme activity (s-ACE), which is elevated in about 60% of sarcoidosis patients. The normal inter-individual biological variation of s-ACE is large. Approximately 50% of the variation is due to a genomic insertion/deletion (I/D) polymorphism in the ACE gene.
  
  
  METHODS
  We searched the MEDLINE library for articles presenting genotype-based reference intervals for s-ACE in healthy people. We summarised the results as weighted mean DD/II ratios of s-ACE. We also summarised the presented frequencies of the genotypes.
  
  
  RESULTS
  We identified nine studies presenting genotype-based reference intervals. All studies found a significant difference between mean s-ACE in the three genotype groups DD, ID and II. The mean DD/II ratio was 1.85 (range: 1.79-1.92) for all studies, 2.01 (1.92-2.10) for Caucasians and 1.64 (1.55-1.73) for Asians. The median frequencies of genotypes among Caucasians were 23% II, 45% ID and 30% DD, and 45% II, 49% ID and 14% DD among Asians.
  
  
  CONCLUSIONS
  Genotyping for the I/D polymorphism increases the benefit of s-ACE since all studies found significantly different levels between genotype groups in healthy subjects. Genotyping is of special value if s-ACE is between the upper 97.5 percentile for genotype II and DD since values in this interval are at risk of being misclassified. Due to assay variation, genotype-specific reference levels should be verified locally.
authors.affiliation: Lungemedicinsk Afdeling LUB, Hjertecentret, Aarhus Universitetshospital, Nørrebrogade 44, 8000 Aarhus C, Denmark. andrniel@rm.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fløe
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Hoffmann
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.forename: Ole
authors.initials: O
authors.lastname: Hilberg
mesh_terms: D044466:Asian People / Q000235:genetics*; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D012016:Reference Values; D012507:Sarcoidosis / Q000097:blood* / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D007703:Peptidyl-Dipeptidase A