ACE I/D-corrected Z -scores to identify normal and elevated ACE activity in sarcoidosis

• Published in: Respiratory medicine 2007-03, Vol.101 (3), p.510-515
• Main Authors: Kruit, Adrian, Grutters, Jan C, Gerritsen, Wim B.M, Kos, Snježana, Wodzig, Will K.W.H, van den Bosch, Jules M.M, Ruven, Henk J.T
• Format: Article
• Language: English
• Subjects: ACE I/D polymorphism; Adolescent; Adult; Aged; Alleles; Angiotensin-converting enzyme; Biological and medical sciences; Female; Gene Deletion; Gene Frequency; Genetic disorders; Genotype; Genotype-corrected reference interval; Hospitals; Humans; Male; Medical sciences; Middle Aged; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - genetics; Pneumology; Polymorphism, Genetic - genetics; Pulmonary/Respiratory; Sarcoidosis; Sarcoidosis - enzymology; Sarcoidosis - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Standard deviation; Standard scores; Z-score
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2006.06.025

Summary Background The value of elevated serum angiotensin-converting enzyme (ACE) activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing debate. This may be at least related to the insertion (I)/deletion (D) polymorphism in the ACE gene (ACE I/D). ACE activity is influenced by the ACE I/D polymorphism. As a consequence, the use of one reference interval instead of three genotype-specific reference intervals for ACE activity may lead to a less precise interpretation of ACE activity. Methods In order to assess whether determination of ACE activity indeed requires the ACE I/D genotype to be taken into account, we established ACE I/D-corrected reference intervals in healthy, Caucasian volunteers ( n =200). In addition, ACE activities in ACE I/D genotyped patients suspected of or having sarcoidosis ( n =129) were expressed as the Z -score related to ACE I/D-corrected reference intervals. Results Comparison of the Z -score with ACE activity in which ACE I/D is ignored rendered 8.5% misclassification of ‘elevated’ versus ‘normal’ ACE or vice versa. Conclusions Our data demonstrate a convenient way to circumvent the use of three reference intervals by introducing a Z -score for ACE activity. It also illustrates the need to re-investigating the possible clinical value of serum ACE activity in sarcoidosis by considering ACE I/D.