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Dan Med J. 2014 May;61(5):A4815.

Genotyping increases the yield of angiotensin-converting enzyme in sarcoidosis--a systematic review.

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Lungemedicinsk Afdeling LUB, Hjertecentret, Aarhus Universitetshospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.



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.


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.


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.


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.

[Indexed for MEDLINE]

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