Elevated Serum Angiotensin-converting Enzyme Activity Research Articles

Extreme elevation of serum angiotensin-converting enzyme (ACE) activity: always consider familial ACE hyperactivity

Measurement of serum angiotensin-converting enzyme (ACE) activity can be helpful in the diagnosis and disease monitoring of sarcoidosis. Elevated serum ACE activity is found in 60-70% of sarcoidosis patients. Usually, the ACE activity is mildly increased (<3-fold the upper limit of the reference range) in sarcoidosis patients. Extremely elevated ACE activity is suggestive of the benign condition known as 'familial hyperactivity of ACE'. Familial hyperactivity of ACE is a relatively rare condition and can be confirmed by genetic testing. Considering a genetic cause of strongly elevated serum ACE activity is important to prevent possible overdiagnostics. Here, we highlight the factors that may complicate the interpretation of serum ACE activity measurements, and we present two cases that illustrate the importance of interdisciplinary consultation when extremely elevated serum ACE activity is measured.

Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population

Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin–angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1–18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD.

Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic tests for serum ACE activity.

The discovery that an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene influences the circulating concentration of ACE may have implications for the proper use of serum ACE activity measurements in screening for sarcoidosis. To determine whether the sensitivity of the serum ACE test improves if ACE genotype is taken into account. A retrospective determination of ACE genotype and clinical diagnosis was done in 54 patients with serum ACE activity above the upper limit of the reference range for the insertion (II) genotype. ACE was measured by radioenzymatic and spectrophotometric techniques, and genotype by PCR. When serum ACE values determined diagnostically were related to the appropriate genotype-specific reference range, sensitivity and specificity for diagnosis of sarcoidosis were 65-70% and 58% respectively, compared to 47-57% and 77% with a reference range unsegregated for genotype. ACE genotyping may be helpful in determining the diagnostic significance of mildly elevated serum ACE activity in patients with the II and ID genotypes.

Serum angiotensin converting enzyme activity in chronic beryllium disease.

Serum angiotensin converting enzyme (SACE) activity is used as a marker of sarcoidosis activity and severity, but in chronic beryllium disease (CBD) the studies of SACE give conflicting results. We examined SACE activity in 23 CBD patients, five patients with beryllium sensitization, and 25 beryllium-exposed control subjects. CBD patients underwent complete clinical evaluation, including physical examination, pulmonary function testing, exercise physiology testing, chest radiography, and bronchoscopy with bronchoalveolar lavage and biopsy. CBD SACE activity was systematically compared with these clinical markers of disease severity. Of CBD patients, 22% had elevated SACE activity. The test did not discriminate CBD patients from those in the beryllium-sensitized or beryllium-exposed groups. However, SACE activity in CBD correlated with the extent of pulmonary granulomatous inflammation as reflected by the symptom of breathlessness, the number of white cells in bronchoalveolar lavage (r = 0.44), the number of lavage lymphocytes (r = 0.58), the lavage lymphocyte percentage (r = 0.55), and the profusion of small opacities on chest radiograph (r = 0.41). The test-retest reliability of the assay was high (r = 0.84), as was the agreement between fresh and -70 degrees C frozen sera (r = 0.93). We conclude that SACE activity levels may reflect the extent of pulmonary granulomatous inflammation in CBD but that the test does not help discriminate disease from nondisease.