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

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.     

Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases

Abstract. Papadopoulos KI, Melander O, Orho‐Melander M, Groop LC, Carlsson M, Hallengren B (University of Lund, Malmö University Hospital, Malmö, Sweden). Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med 2000; 247: 71–77. Objectives. To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis. Design. In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17). Settings. The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. Subjects. Sixty‐two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19–75 years, median age/range at study 47.5/22–81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40–82 years) served as controls. Results. S‐ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S‐ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy–Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over‐represented in X‐ray stage III compared to the other X‐ray stages (P = 0.0181) and a significant increase in the DD genotype in X‐ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected. Conclusion. We confirmed that the S‐ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S‐ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X‐ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S‐ACE it encodes.     

Serum Lysozyme Levels and Clinical Features of Sarcoidosis

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0.05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases. Accepted for publication: 19 November 1998     

Elevated ACE activity is not associated with asthma, COPD, and COPD co-morbidity

The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for risk of asthma, COPD, and COPD co-morbidity. In 9034 Danish adults, we determined whether individuals homozygous or heterozygous for the ACE D allele are at greater risk of asthma, COPD, or COPD co-morbidity compared with ACE II homozygous individuals. In the general population, serum ACE activity increased with the number of D alleles (Kruskal-Wallis ANOVA: II vs. ID, p < 0.001; ID vs. DD, p < 0.001); however, this did not translate into altered risk of asthma or COPD. In the general population, the odds ratio (95% confidence interval) for asthma was 1.2 (0.9–1.4) for ID individuals and 1.2 (0.9–1.5) for DD individuals compared with II individuals. In the general population, the odds ratio for COPD was 0.9 (0.8–1.1) for ID individuals and 1.0 (0.8–1.2) for DD individuals compared with II individuals. Among patients with COPD, the odds ratio for ischemic heart disease was 1.1 (0.8–1.6) for ID individuals and 1.2 (0.8–1.7) for DD individuals compared with II individuals; corresponding odds ratios for hypertension were 1.1 (0.7–1.5) and 0.8 (0.5–1.2), and for low physical activity 0.9 (0.5–1.4) and 0.7 (0.4–1.2). The results were similar upon adjustment for sex, age, smoking status, body mass index, total cholesterol, and ACE inhibitor/angiotensin II type 1 receptor blocker use. These data suggest that lifelong genetically elevated ACE activity is not a major risk factor for asthma or COPD, or for ischemic heart disease, hypertension, and low physical activity in COPD patients.     

Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis

OBJECTIVES: The aim of this study was to test for genetic linkage and association between polymorphisms of the angiotensin-converting enzyme (ACE) gene and familial occurrence of sarcoidosis. DESIGN, SETTING AND SUBJECTS: German families with more than one member suffering from sarcoidosis were contacted and a DNA bank was established. Sixty-two families (140 patients, 77 females and 63 males, and 104 unaffected relatives) were genotyped for the ACE gene insertion/deletion (I/D) polymorphism and for two flanking variable sites (ACE A-5466C and ACE 4656(CT)2/3). As controls, 100 DNAs from unrelated resident Caucasians (50 females, 50 males) were analysed. ACE allele and genotype frequencies were determined, and parametric linkage and affected sib pair analyses and transmission disequilibrium tests were performed. RESULTS: There was a striking over-representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature. The same was evident for the accompanying genotypes CC and 2,2 of the flanking polymorphisms. Linkage between the segregation of ACE alleles and the disorder within families was clearly excluded for simple models of inheritance. However, there was a suggestive but not significant (P = 0.06) excess of allele sharing amongst affected siblings. There was no transmission disequilibrium for any ACE allele or haplotype. CONCLUSIONS: ACE is involved in the pathogenesis of sarcoidosis, but the ACE polymorphisms are not an inherited main cause of the disease. They are more likely to modify the development of the disorder, and the ACE I/D genotype DD might be a promoter to clinical manifestation.     

The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis

Background: The butyrophilin‐like 2 (BTNL2) gene is located on chromosome 6p21.3 close to the HLA‐class II genes. An association has been reported between sarcoidosis and a single nucleotide polymorphism in BTNL2, rs2076530, also termed the A allele. Objectives: To evaluate whether patients with sarcoidosis carry the A allele more frequently than healthy subjects. Methods: The series comprised 87 ethnic Danes with sarcoidosis and 113 healthy control subjects. Analysis of rs2076530 was performed by Taqman assay, polymerase chain reaction and sequencing of genomic DNA. Results: Sarcoidosis patients had a higher frequency of the A allele than controls (73.9% vs 55.8%) (P < 0.025). The frequency of GG, GA and AA genotype was 5.7%, 40.2% and 54.0% in patients vs 16.0%, 56.6% and 27.4% in controls (P < 0.001). The AA genotype was associated with increased risk of sarcoidosis in both a dominant [odds ratio (OR) 3.1; 95% confidence interval (CI) 1.1–8.7; P < 0.03] and a recessive model (OR 3.1; 95% CI 1.72–5.61; P < 0.001). Population attributable fraction for disease was 50% in a dominant model and 25% in a recessive model. Conclusions: The BTNL2 A allele variant occurs with a high frequency in Danish patients with sarcoidosis and the AA genotype is associated with a ～threefold higher risk of sarcoidosis than the GG genotype. Our results should encourage future studies on the interrelationship between the BTNL2 protein and granuloma formation in sarcoidosis. Please cite this paper as: Milman N, Svendsen CB, Nielsen FC and Hansen TvO. The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis. Clin Respir J 2011; 5: 105–111.     

Angiotensin-converting enzyme gene polymorphism,left ventricular remodeling,and exercise capacity in strength-trained athletes

The mechanisms that regulate the development of human physiological cardiac hypertrophy remain poorly understood. The renin-angiotensin system, which is modulated by genetic polymorphism, plays an important role in the regulation of vascular tone and myocardial hypertrophy. Although a few studies have analyzed the association of angiotensin-converting enzyme (ACE) polymorphism and left ventricular (LV) hypertrophy in isotonic exercise-trained subjects who developed eccentric cardiac hypertrophy, there has been no research done in power athletes who developed concentric cardiac hypertrophy. We have hypothesized that ACE genotypic modulation characteristics may affect LV mass in power athletes. This study included 29 elite Caucasian wrestlers (mean age, 22.6 years) and 51 age-matched sedentary subjects. According to the absence or presence of the insertion segment in the polymerase chain reaction (PCR) product, the subjects were classified as homozygous deletion-deletion (DD), insertion-insertion (II), or heterozygous insertion-deletion (ID). The association of LV hypertrophy with ACE gene insertion/deletion (I/D) polymorphism was analyzed. Left ventricular mass and index were determined by echocardiography. Angiotensin-converting enzyme genotyping was performed on peripheral leukocytes using the polymerase chain reaction technique. The study and control group subjects were similar in height and weight. Left ventricular hypertrophy in the athletes was more apparent than in the controls. Angiotensin-converting enzyme genotype II frequency was 17.2% (5) in the athletes, 17.6% (9) in the controls; ID frequency was 51.7% (15) in the athletes, 56.8% (29) in the controls; and the DD frequency was 31% (9) in the athletes and 25.4% (13) in the controls. Left ventricular mass and mass index were found to be higher in genotype DD (126.2 ± 2.9g/m²) than genotype II (85.5 ± 4.0g/m²) or genotype ID (110.1 ± 2.3g/m²) in the athletes (P < 0.001). Furthermore, maximal oxygen consumption in genotype DD was found to be higher than in II and ID. An association was found between ACE gene I/D polymorphism and LV hypertrophy in strength-trained athletes.     

冠心病患者血管紧张素转换酶基因多态性及其与血清血管紧张素转换酶水平的关系

为研究冠心病患者血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性分布及其与血清ACE水平的相关性，应用多聚酶链反应方法测定了61例冠心病患者和63例健康人群的ACE基因I／D多态性，并采用微量比色法测定其血清ACE水平。结果发现，冠心病患者ACE基因DD型出现频率显著高于对照组，且DD基因型者具有较高的血清ACE水平。提示ACE基因I／D多态性与血清ACE水平密切相关，DD型ACE基因可能是中国人冠心病发病的独立危险因子。     

冠心病患者血管紧张素转换酶基因多态性及其与血清血管紧张素转换酶水平的关系

为研究冠心病患者血管紧张素转换酶（ＡＣＥ），基因插入／缺失（Ｉ／Ｄ）多态性分布及其血清ＡＣＥ水平的相关性，应用多聚酶链反应方法测定了６１例冠心病患者和６３例健康人群的ＡＣＥ水平，结果发现，冠心病患者ＡＣＥ基因ＤＤ型出现频率显著对照组，且ＤＤ基因型者具有较高的血清ＡＣＥ水平，提示，ＡＣＥ基因Ｉ／Ｄ多态性与血清ＡＣＥ水平密切相关，ＤＤ型ＡＣＥ基因可能是中国人冠心病发病的独立危险因子。     

Differences in angiotensin convertase enzyme (ACE) activity and expression may contribute to shorter event free period after coronary artery bypass graft surgery

Aims: The goal of this study was to investigate the importance of the vascular angiotensin convertase enzyme (ACE) in coronary artery bypass graft surgery (CABG) patients. Methods: Vascular tissue (distal saphenous vein [n= 163] and/or radial artery [n= 120] segments) and blood samples were collected from CABG patients (n= 81). We studied (i) the potency of angiotensin I (AngI) and angiotensin II (AngII) to evoke vascular contractions; (ii) vascular and plasma ACE concentrations; and (iii) ACE genotype of the patients enrolled. Results: The ratio of the potencies (EC₅₀) of AngII and AngI was significantly lower in radial artery compared to the saphenous vein (0.17 ± 0.03 nM and 0.51 ± 0.14 nM, respectively, P= 0.003), suggesting a 3‐fold more effective AngI conversion in saphenous vein samples. Angiotensin constrictions were inhibited with telmisartan and captopril in both saphenous veins and radial arteries. Vascular ACE expression was significantly higher in saphenous vein compared to radial artery (9.7 ± 1.0 ng/mg and 5.3 ± 0.7 ng/mg, respectively, P= 0.01). Serum but no tissue ACE concentration was determined by ACE insertion/deletion polymorphism. Accordingly, no relation was found between serum and tissue ACE expression. Conclusion: ACE‐inhibitor therapy targeting tissue located ACE may be beneficial to patients with saphenous vein grafts after CABG surgery.     

Identification of Active Sarcoidosis Using Chitotriosidase and Angiotensin-Converting Enzyme

Purpose

Activity/remission differentiation is a great challenge in the follow-up and treatment of sarcoidosis patients. Angiotensin-converting enzyme (ACE) and high sensitivity C-reactive protein (hs-CRP) were proposed as sarcoidosis biomarkers. More recently, chitotriosidase (CHITO) has been described as a better alternative. This study has the aim to evaluate the association of CHITO activity, ACE, hs-CRP or a combination of these biomarkers and to construct a clinical algorithm to differentiate between sarcoidosis activity/remission status.

Methods

Forty-six patients with either active sarcoidosis or sarcoidosis in remission and 21 healthy individuals were included. ACE, hs-CRP, and CHITO were evaluated in serum samples. Comparisons of the laboratory variable means among groups were performed by linear models. The cutoff points of the biomarkers for activity/remission differentiation were calculated using the Youden’s index. Biomarker cutoff points and decision tree classifier (DTC) performance were estimated by their leave-one-out cross-validation (LOOCV) accuracy (Acc), sensitivity (Se), and specificity (Sp).

Results

A 55% mean Se and a 100% mean Sp were found for CHITO, while an 88% Se and a 47% Sp were found for ACE, and a 66% Se and a 68% Sp for hs-CRP cutoff points for activity/remission differentiation. The DTC algorithm with CHITO, hs-CRP, and ACE information had an LOOCV mean Acc of 82%, Se of 78%, and Sp of 89% for sarcoidosis activity/remission differentiation.

Conclusions

The algorithm involving CHITO, hs-CRP, and ACE could be a suitable strategy for differentiation between sarcoidosis activity/remission status.

     

An angiotensin-converting enzyme (ACE) inhibitor in human serum. Increased sensitivity of the serum ACE assay for detecting active sarcoidosis

Measurement of serum angiotensin-converting enzyme (ACE) is extremely useful as an aid in the diagnosis and longitudinal evaluation of patients with sarcoidosis. We have detected a human serum ACE-inhibitor which affects the ACE level obtained by activity measurements. The effect of the inhibitor can be eliminated by a mere eight-fold dilution of the serum sample with physiologic saline. We recommend that serum ACE be performed with 1:8 dilutions of serum to eliminate the effect of the ACE inhibitor. The inhibitor has a MW above 50,000 daltons, and reversibility of inhibition by dilution appears to be ion dependent. Dialysis of an inhibitor-containing serum sample against saline causes the inhibition to become irreversible, allowing the distinction between alinearity of the assay vs an inhibitor effect when a serum has ACE activity greater than 50 units/ml. The source of the serum ACE-inhibitor remains to be determined.     

Elevated serum angiotensin-converting enzyme activity in onchocerciasis

Our objective was to measure serum angiotensin-converting enzyme (ACE) activity in patients with onchocerciasis. Serum ACE activity is commonly used in the diagnosis and follow-up of patients with sarcoidosis. However, serum ACE activity can also be elevated in a number of other granulomatous disorders. In onchocerciasis, a parasitic disease affecting millions of people in Africa and Central and South America, granulomatous tissue around adult worms has been identified, yet raised serum ACE activity has not been reported so far. We measured serum ACE activity in serum samples from 42 onchocerciasis patients and 39 endemic controls previously enrolled in two studies concerning the side effects after ivermectin treatment in Sierra Leone, West Africa. The mean ACE activity in the patient group was 53.8 units/liter (S.D. 19.8) compared with 35.2 units/liter (S.D. 14.0) in the control group (p < 0.0001). Nine of 42 patients had elevated ACE activity (mean of the endemic controls ± 2 S.D.) compared with 1 of 39 controls (p = 0.01). Sensitivity and specificity of elevated ACE in serum from onchocerciasis patients from Sierra Leone was 21 and 97%, respectively. ACE activity was not related to the microfilarial skin load or development of side effects after ivermectin treatment. Serum ACE activity can be elevated in onchocerciasis. Clinicians should be aware of this phenomenon when determining serum ACE activity in persons from endemic areas. Offprint requests to: Marjolein J. H. Ronday     

Genotype-corrected reference values for serum angiotensin-converting enzyme.

The deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene has the greatest impact on serum ACE level in Caucasians of any factor yet discovered. The aim of the present study was to establish new ACE genotype-corrected normal ranges for serum ACE level in a population of central European origin. After a medical examination, 159 healthy Caucasians volunteered to donate blood for the study. ACE genotypes were assessed by PCR and serum ACE levels were determined using two different kinetic tests. The distribution of the D/I polymorphism of the ACE gene was in accordance with the Hardy-Weinberg equilibrium. Serum ACE levels and ACE genotypes correlated significantly, with the highest serum ACE levels in subjects with ACE genotype D/D, and the lowest serum ACE levels in subjects with genotype I/I (mean+/-sd, assay 1: D/D 59.3+/-15.1 U x L(-1), D/I 45.5+/-15.2 U x L(-1), I/I 34.8+/-13.7 U x L(-1); assay 2: D/D 43.7+/-14.1 U x L(-1), D/I 33.7+/-12.1 U x L(-1), I/I 25.4+/-9.5 U x L(-1)). Although they gave different absolute values of serum ACE levels, the results of the two test kits correlated significantly. In conclusion, the present authors recommend the use of new, genotype-specific reference values for serum angiotensin-converting enzyme levels, especially to improve the sensitivity and specificity of tests for angiotensin-converting enzyme in the follow-up of sarcoidosis.     

ACE deletion polymorphism is associated with a high risk of non-infectious pulmonary complications after stem cell transplantation

Non-infectious pulmonary complication (NIPC) is a serious adverse event for allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. NIPC includes both categories of lung complications: early onset idiopathic pneumonia syndrome (IPS) (onset <120 days) and late-onset non-infectious pulmonary complications (LONIPCs). Both categories have high mortality and morbidity rates, and critical treatments are not available. The renin–angiotensin system plays a critical role in pulmonary fibrosis. We, therefore, studied the relationship between angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphisms and NIPC incidence in 149 consecutive allo-HSCT recipients. A total of 12.1 % (18/149) of these patients were diagnosed with NIPC (IPS, 3; LONIPCs, 15). Eight NIPC patients died from respiratory failure (mortality rate, 44.4 %). Peripheral blood stem cell transplantation was associated with a significantly higher incidence of NIPC than bone marrow transplantation and cord blood transplantation by univariate analysis (HR 3.13, P = 0.031). The serum ACE levels differed significantly according to the ACE insertion/deletion polymorphism. Patients with an ACE D/D genotype occurred at a significantly higher frequency among NIPC patients than I/D and I/I patients (HR 9.03, P < 0.0001). Multivariate analysis confirmed that NIPC is associated with ACE D/D genotypes (HR 8.8, P < 0.001). Our data support a role for the renin–angiotensin system in the pathogenesis of NIPC after allo-HSCT, and may represent a therapeutic target for complications.     

Angiotensin Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism,and Diabetic Retinopathy in Subjects with IDDM and NIDDM

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 ± 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 ± 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p <0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of ***I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE ***I/D genotype was similar in subjects with IDDM, NIDDM, and controls (χ² = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (χ² = 3.42, df = 2, p = ns) or NIDDM (χ² = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (χ² = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.     

A Clinical Evaluation of Serum Angiotensin Converting Enzyme in Sarcoidosis

Summary: Angiotensin converting enzyme was measured in the serum of 52 patients with sarcoidosis, 67 healthy control subjects and 64 patients with pulmonary and non-pulmonary diseases. The patients with sarcoidosis were classified on clinical grounds as having active or inactive disease.
In 26 patients with active sarcoidosis not taking corticosteroids the mean serum ACE was significantly higher than in normal controls (P < 0.001). 73% of these patients had elevated serum ACE. Only two out of 12 (17%) patients with inactive sarcoidosis not taking corticosteroids had elevated serum ACE. Serum ACE was normal in patients taking oral corticosteroids for longer than two weeks.
Eighty per cent of patients with active sarcoidosis with radiological evidence of pulmonary parenchymal involvement had an elevated serum ACE compared to 25% in patients with normal chest X-rays and 60% of those with bilateral hilar lymphadenopathy.
All sarcoid patients with hypercalcaemia had elevated serum ACE whereas only half of those with normal serum calcium had elevated ACE.
In the patients with other thoracic and granulomatous conditions serum ACE was normal or rarely marginally elevated.
Serum ACE appears to be of value in the diagnosis of active sarcoidosis.     

Significance of elevated serum ACE in pneumology

Angiotensin-converting enzyme (ACE) levels were measured in the serum of patients with various pulmonary affections (sarcoidosis, tuberculosis, anthracosilicosis, cancer, etc.), with diabetes or renal insufficiency, and in 247 healthy subjects. Mean ACE levels (41.5 U/ml +/- 16) were significantly higher in sarcoidosis than in normal controls (22 U/ml +/- 6), high values (greater than or equal to 34 U/ml) being observed in 62 p. cent of cases. In these patients, the ACE tended to become normal in parallel with clinical and radiological improvement in the disease, and to increase again during relapses. In 75 p. cent of sarcoidosis patients there was concordance between the increase in alveolar lymphocytes and that of serum ACE. Elevated ACE levels were noted in only 3 p. cent of non-sarcoidosis pneumopathies, and in 24 and 18 p. cent of diabetes and renal insufficiency cases respectively. In the absence of these two latter affections, measuring ACE levels is of obvious value for the diagnosis and follow-up surveillance of sarcoidosis.     

Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype

OBJECTIVES: The objective of this study was to assess whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influences the adequacy of the neurohormonal response to ACE inhibitors in patients with chronic heart failure (CHF). BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of CHF, and aldosterone levels closely relate to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevated serum levels of aldosterone despite long-term administration of apparently adequate doses of these agents. METHODS: We prospectively studied 132 patients with CHF (ejection fraction <45%) receiving long-term therapy with ACE inhibitors for over six months. Patients taking aldosterone antagonists were excluded from the study. "Aldosterone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were then divided into two subgroups according to the presence (group 1) or absence (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polymorphism was performed by polymerase chain reaction. RESULTS: The prevalence of aldosterone escape in our patients was 10% (13/132). The two groups of patients did not differ regarding the dose of ACE inhibitor, diuretics and their renal function. There was a statistically significant different distribution of genotypes between the two groups, with a higher proportion of DD genotype in group 1 compared with group 2 (62% vs. 24%, p = 0.005). CONCLUSIONS: Patients with CHF with aldosterone escape have a higher prevalence of DD genotype compared with patients with aldosterone within the normal limits. Angiotensin-converting enzyme gene polymorphism contributes to the modulation and adequacy of the neurohormonal response to long-term ACE-inhibitor administration in CHF.     

ACE基因I/D多态性与系统性红斑狼疮肾脏易感性关系的研究

研究血管紧张素转换酶基因Ｉ／Ｄ多态性与系统性红斑狼疮肾脏易感性的关系。方法用ＰＣＲ法和比色法分别测定５８例ＳＬＥ患者和４０例正常人的ＡＣＥ基因型和血清ＡＣＥ活性。结果确诊ＳＬＥ时临床有肾脏受累表现组ＡＣＥ基因ＤＤ型和Ｄ等位基因分布频率明显高于组，且ＤＤ型、ＤＩ型者血清ＡＣＥ活性前者明显于高于后者。