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

INTRODUCTION 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. CONCLUSION 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.