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1.
Background: 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. Aim: To determine whether the sensitivity of the serum ACE test improves if ACE genotype is taken into account. Methods: 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. Results: 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. Conclusion: ACE genotyping may be helpful in determining the diagnostic significance of mildly elevated serum ACE activity in patients with the II and ID genotypes. 相似文献
2.
Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease. 相似文献
3.
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. 相似文献
4.
Angiotensin-converting enzyme (ACE) levels and ACE gene polymorphisms have been related with hypertension but with contradictory results between populations. We have investigated the association among the allelic distribution of the insertion-deletion (I/D) polymorphism of the ACE gene, identified by polymerase chain reaction (PCR), serum ACE activity determined by spectrophotometry, and the blood pressure (BP), in a Mediterranean population in the southwest of Europe. A total of 1322 randomised individuals were analysed, and a comparative study was conducted analysing 205 individuals from the group with highest BP (fifth quintyl) and 196 from the group with lowest BP (first quintyl). In addition we have studied the frequencies of alleles in separated groups of women and men. We conclude that in this population there is no association between I/D polymorphism and hypertension. However, we have found a statistically significant association between the presence of the D allele in the genotypes and an elevation of serum ACE activity. 相似文献
5.
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. 相似文献
6.
The angiotensin-1-converting enzyme (ACE) gene has been suggested to be involved in the development of metabolic syndrome (MetS). However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the association between ACE insertion/deletion (I/D) polymorphism and MetS. Published literature from PubMed, EMBASE, and ISI Web of Science databases was searched for eligible publications. All studies assessing the association between ACE I/D polymorphism and MetS were included. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. Ten studies (1939 cases/2845 controls) for ACE I/D polymorphism were included in this meta-analysis. Most of the studies were performed in whites. The ACE I/D polymorphism was associated with an increased OR of MetS under a dominant model (DD + ID vs II: OR = 1.39; 95% CI, 1.22-1.60; P < .001). Using this model, similar results were found among studies using different ethnic populations, studies using different MetS definitions, and studies with more than 100 cases. This meta-analysis indicated that the D allele of the ACE gene, known to be related to higher levels of angiotensinogen, is associated with an increased OR of MetS. However, given the limited sample size, this association warrants further investigation. 相似文献
7.
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. 相似文献
8.
An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene determines serum ACE levels. The D allele is associated with increased ACE activity and is linked to cardiovascular disease. Hormone replacement therapy (HRT) in postmenopausal women (PMW) decreases serum ACE activity and concomitantly increases plasma bradykinin. We investigated the effect of HRT on these parameters in PMW according to ACE-genotype. We assessed 68 PMW during 12-month oral HRT (0.625 mg conjugated estrogen +2.5 mg medroxyprogesterone acetate). ACE genotype was determined at baseline, and serum ACE activity and plasma bradykinin were measured at baseline and after 3-, 6-, and 12-month HRT. We divided the PMW into three groups according to ACE genotype: groups I/I (n = 26), I/D (n = 33), and D/D (n = 9). HRT resulted in a significant reduction in the genotype-associated increase in ACE activity in the ACE I/D and D/D groups after 6-month (p < 0.001 and p < 0.05, respectively) and 12-month HRT (p < 0.001 and p < 0.01, respectively), but not in the I/I group. While the reduction of ACE activity was expected to increase bradykinin in the ACE I/D and D/D groups, HRT significantly increased the bradykinin levels not only in these two groups but also in the ACE I/I group at both 6 months (p < 0.01, p < 0.05, and p < 0.001, respectively) and 12 months after the start of HRT (p < 0.01, p < 0.01, and p < 0.01, respectively). These results suggest that the increased plasma bradykinin of PMW by HRT might not be induced solely by the reduction in serum ACE activity. 相似文献
9.
Essential arterial hypertension often predisposes patients to prothrombotic state and increased risk of vascular and organ complications. Vital role in regulation of hemostatic processes is played by genetic factors, renin-angiotensin system and disorders of lipid metabolism. Prime genetic factors involved in the process are 4G/5G polymorphism of promoter region coding tissue plasminogen activator inhibitor-1 (PAI-1) and I/D polymorphism for angiotensin converting enzyme (ACE) gene. The aim of work was the evaluation of alterations within fibrinolysis system (estimation of t-PA and PAI-1 levels), fibrinogen concentration (Fb) and ACE activity with regard to co-existent dyslipidemia and features of left ventricle hypertrophy (LVH). Moreover the analysis of influence of 4G/5G PAI and I/D ACE gene polymorphism on intensification of aforementioned alterations among hypertensive patients was performed. Research was carried out in 170 subjects under 40 years old, in two study groups, HT-- hypertensive group--125 patients with previously untreated hypertension without clinical features of ischaemic heart disease and NT--45 normotensive, healthy subjects. HT group has been further divided into four subgroups: DLP (dyslipidemic, n = 51), NLP (normolipidemic n = 74), LVH+ (with features of left ventricle hypertrophy, n = 35), LVH (-) (without features of left ventricle hypertrophy, n = 90). In a whole HT group significantly higher levels of PAI-1, t-PA and Fb were noted in comparison to NT group, considerably more pronounced within DLP rather than NLP subgroups. Moreover, pronounced increase in ACE activity was recorded in DLP and LVH+ subgroups. It has been proved that 4G/4G homozygous subjects of 4G/5G PAI-1 gene polymorphism from HT group tend to present higher levels of PAI-1 and t-PA if contrasted to 4G/4G genotype of NT group, with more distinct effect within DLP subgroup. Carriers of D allele (genotypes I/D, D/D) of I/D ACE gene polymorphism from HT group characterise with significantly higher activity of ACE in contrast to I/I genotype of HT group, with particularly marked effect in DLP and LVH+ subgroups. Basing on above mentioned results it may be concluded that essential hypertension (especially if complicated with dyslipidemia) impairs fibrinolysis, what might be related to renin-angiotensin system activation in lipid metabolism disorders. Deletion alleles of 4G/5G polymorphism (4G allele) and I/D polymorphism (D allele) in patients with hypertension independently modify fibrinolysis towards prothrombotic state with more distinct effect in dyslipidemia. Increased activity of ACE in D allele carriers may predispose to left ventricle hypertrophy. 相似文献
10.
血管紧张素转换酶(ACE)在肾素-血管紧张素-醛固酮系统(RASS)和激肽释放内原-激肽系统(KKS)中发挥着重要的作用。近年研究发现,ACE通过不同的遗传机制在心脑血管疾病的发生发展中发挥作用,其多态性决定了血浆和细胞内ACE浓度,是研究各类心脑血管疾病遗传易感性的候选基因,本文通 相似文献
11.
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。 相似文献
12.
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。 相似文献
13.
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。 相似文献
14.
OBJECTIVE: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with different serum ACE concentrations and cardiac ACE activity. We assessed whether the ACE gene I/D polymorphism influenced cardiac mortality in Japanese patients with acute myocardial infarction. METHODS AND RESULTS: The ACE gene I/D polymorphism was determined in 441 consecutive patients with a first myocardial infarction.There were 69 patients (16%) with the DD genotype, 194 patients (44%) with the ID genotype, and 178 patients (40%) with the II genotype. During a mean follow-up of 9.4 months, there were 49 cardiac deaths (DD, n = 4; ID, n = 26; II, n = 19).The DD genotype was significantly associated with a lower mortality than the other genotypes (p = 0.0363) by Cox regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. CONCLUSIONS: In a selected cohort of Japanese patients, the DD genotype was associated with a significantly lower cardiac mortality after a first myocardial infarction. 相似文献
15.
BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism. 相似文献
16.
Background: Renin-angiotensin system (RAS) is a complex network of enzymes and peptides with the essential role in blood pressure control. The relationships between RAS components, RAS-related genetic polymorphisms and therapy response in essential hypertension (EH) were widely explored but the results were inconclusive. Aim: The aim of this study was to explore the functional role of ACE insertion/deletion (I/D) polymorphism on the systemic quantity of angiotensin-converting enzyme (ACE), its homolog - ACE2, chymase and angiotensin II in EH patients with respect to achieved therapeutic blood pressure control. Results: Genotyping of ACE I/D polymorphism was performed among 140 patients with EH from Bulgaria. The serological analyses reveal the significant elevation of the serum quantity of all investigated enzymes in EH than normotensive controls. In addition, serum ACE2 (183.57 pg/ml; vs. 151.78 pg/ml; p = 0.02) and chymase (68.5 pg/ml; vs. 23.66 pg/ml; p = 0.034) were significantly higher in patients with uncontrolled EH than controlled EH in response to ACE-inhibitory therapy. Also, ACE I/D polymorphism showed a significant impact on the serum ACE and chymase levels. ACE quantity was the highest among carriers of DD-genotype, followed by ID and II-genotype. Contrary, chymase was in the highest quantity in II-genotype compared to ID-genotype (p = 0.025) and DD-genotype (p = 0.044). Conclusions: Our results suggest that insufficient blood pressure control by ACE-inhibitory therapy could be associated with elevation of serum ACE2 and chymase levels. Also, it appears that ACE I/D polymorphism may influence the circulating quantity of chymase in addition to ACE. 相似文献
17.
The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with a 3.2 to 6.8-fold increased risk of severe hypoglycemia in type 1 diabetes. This relationship has not been assessed in type 2 diabetes. We aimed to test for association of the ACE I/D polymorphism with severe hypoglycemia in type 2 diabetes. Patients with type 2 diabetes (n = 308), treated with insulin (n = 124) or sulphonylureas (n = 184), were classified according to whether or not they had previously experienced severe hypoglycemia. Samples of DNA were genotyped for the ACE I/D polymorphism using two alternative polymerase chain reactions to prevent mistyping due to preferential amplification of the D allele. Overall, 12% of patients had previously experienced one or more episodes of severe hypoglycemia. This proportion did not differ between genotype groups (odds ratio (95% confidence limits) for carriers of D allele relative to II homozygotes: 0.79 (0.35-1.78)). This study found no evidence for association of the ACE I/D polymorphism with severe hypoglycemia frequency in patients with type 2 diabetes. However, we cannot rule out a smaller effect (odds ratio = 1.78). Our results suggest that any effect of ACE genotype on severe hypoglycemia risk in type 2 patients is likely to be smaller than that seen in type 1 diabetes. We recommend future larger-scale studies. 相似文献
18.
The value of different factors are examined to assess activity in 60 patients with biopsy-proven sarcoidosis. In patients with active sarcoidosis (n = 35), 67Gallium scans proved to be the most sensitive method (94 percent sensitivity), followed by serum angiotensin I converting enzyme (S-ACE) levels, chest x-ray films, and lymphocyte assays. In patients with peripheral pulmonary lesions, chest x-ray films failed in 32 percent of cases to document activity (68 percent sensitivity) whereas 67Ga scans and S-ACE levels remained to give reliable results. Despite poor specificity, negative 67Ga scans together with normal ACE levels have a high predictive value for exclusion of active sarcoidosis. In patients with peripheral pulmonary lesions, chest roentgenography is of doubtful value for staging lung involvement and assessment of activity including monitoring and control of therapy. 相似文献
19.
目的 :评价阻塞性睡眠呼吸暂停 (OSA)合并高血压(HT)与血管紧张素转换酶 (ACE)基因多态性的关系。方法 :采用病例对照研究方法 ,以 OSA的严重程度将研究对象分为正常对照组 (6 8人 )、HT组 (45人 )、轻度 OSA合并 HT组 (2 7人 )、中重度 OSA合并 HT组 (31人 ) ,共 171例 ;(2 )观察 ACE I/ D多态在一个 OSA典型家系中的分布。结果 :(1) ACE I/ D等位基因的频率分布如下 :中重度 OSA合并 HT组 ,I等位基因的频率显著高于其他各组 (P<0 .0 0 1) ;而正常对照组、HT组和轻度 OSA合并 HT组之间 I等位基因频率分布没有显著性差别 ;(2 )在一个典型 OSA家系中 I等位基因呈高频率出现。结论 :ACE基因 I等位基因与中重度 OSA显著相关 ,遗传因素是影响中重度 OSA合并 HT发病的重要因素 相似文献
20.
The possible association between the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene and left ventricular hypertrophy (LVH) was investigated in a group of essential hypertensive patients. Seventy-one essential hypertensive patients (35 men and 36 women), aged 51 +/- 1 years, were genotyped by PCR for the I/D polymorphism of the ACE gene. Cardiac morphology and function were assessed by means of M-mode echocardiography. The relative frequencies of the three genotypes, DD, DI, and II, were respectively: 24%, 55%, and 21%. Mean values of left ventricular mass index were 145, 144, and 150 g/m2 for DD, DI, and II genotypes, without significant differences among them (P = 0.82). Likewise, the prevalence of LVH (76%, 64%, and 87%) was not significantly different among the three genotypes (P = 0.23). We conclude that the ACE gene I/D polymorphism is not associated with LVH in essential hypertension. Journal of Human Hypertension (2000) 14, 47-49. 相似文献
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