The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism

ACE displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation, thus possibly promoting venous thromboembolism (VTE). The ACE gene contains an insertion (I) or deletion (D) polymorphism accounting for 50% of the variation in serum ACE concentration. To evaluate the role of the I/D polymorphism in VTE, its prevalence was determined in 931 patients with VTE and 432 blood donors. The prevalence of the DD genotype was 27.6% in patients and 21.3% in controls (OR 1.4; p < 0.02). In multivariate analysis there was a trend of the DD genotype to be an independent risk factor (OR 1.4; p = 0.08). No differences in DD genotype prevalence according to exogenous risk factors were found. Coinheritance of FV G1691A, PT G20210A mutation, and PS deficiency with the DD genotype increased the relative risk of VTE. Thus, the ACE DD genotype is a moderate risk factor of hereditary thrombophilia. Exogenous risk factors did not alter the manifestation of VTE among carriers of the DD genotype, whereas coinheritance of the DD genotype with the aforementioned defects increased the risk for VTE considerably.     

遗忘型轻度认知障碍与血管紧张素转换酶的基因多态性和血清水平关系的研究

目的 探讨遗忘型轻度认知障碍(aMCI)与血管紧张素转换酶(ACE)基因插入和缺失(I/D)多态性及血清ACE活力水平的关系.方法 对符合美国Meyo诊所Petersen等制定的aMCI诊断标准的90例aMCI患者(aMC[组)及90名与aMCI组相匹配正常对照者(对照组)进行神经认知功能评估,并应用聚合酶链反应检测ACE基因I/D多态性,用紫外分光光度法检测血清ACE活力水平.结果 (1)aMCI组的各项神经认知测试成绩均差于对照组(P<0.01).(2)aMCI组ACE基因型(χ2=1.510)及等位基因频率(χ2=6.945)与对照组的差异均有统计学意义(P<0.01),其中aMCI组DD基因型(23%)及D等位基因频率(57%)高于对照组(分别为16%和43%).(3)两组DD基因型(n=35)及DI基因趔(n=109)者的听觉词语记忆、符号数宁转换测试、复杂图形及类别词语流畅性得分低于Ⅱ基因型者(n=36;均P<0.05-0.01).(4)aMCI组(F=7.491)和对照组(F=4.970)ACE基因型各亚组问血清ACE活力水平的差异均有统计学意义(P<0.01),两组ACE活力水平均为DD型组>DI型组>II型组.(5)aMCI组血清ACE活力与听觉词语记忆测试的延迟回忆得分呈负相关(r=-0.249,P<0.05).结论 D等位基因可能为aMCI的发病危险因子,其调控的血清ACE高活力水平与aMCI患者情节记忆损害有关.     

Polymorphism of the angiotensin-converting enzyme gene in patients with cerebral infarction in koreans

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (X ²=0.128, p=0.720). The frequencies of the genotypes of the ACE gene were II:39.6%, ID:45.3%, and DD:15.1% in patients, and II:37.1%, ID:47.6%, and DD:15.3% in controls (X ²=0.127, p=0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.     

Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis

Background: Many studies investigated the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and migraine, with controversial results. Thus, we performed a meta-analysis to better evaluate the correlation of this polymorphism and migraine. Methods: We retrieved studies published up to September 2014 about the ACE gene polymorphism and migraine from electronic database. Pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated to examine the strength of association between the ACE I/D polymorphism and migraine, using random-effects models. Results: We identified 14 separate studies, in which 7334 migraineurs and 22 990 healthy controls were eligible for the meta-analysis. The results showed no relationship between the ACE I/D polymorphism and any migraine. Stratification revealed a protective effect in the Turkish population against migraine with aura for the II genotype model (II vs. DD: pooled OR = 0.366, 95% CI = 0.137–0.980; II vs. DI + DD: pooled OR = 0.370, 95% CI = 0.145–0.945). Similar results were obtained for Turkish people with migraine without aura (II vs. DD: pooled OR = 0.386; 95% CI = 0.166–0.900; II vs. DI + DD: pooled OR = 0.347; 95% CI = 0.156–0.773). Conclusions: The data suggest that the ACE II genotype could exert a protective effect against migraine with aura and without aura at least in the Turkish population.     

Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischaemic stroke.

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with increased incidence of stroke in some populations, although contradictory results have been reported. The aim of this study was to determine the allelic frequency and the genotypic distribution for ACE gene polymorphism in Turkish patients with ischemic stroke compared to appropriate healthy controls and to correlate the genetic findings with stoke type. One hundred and eight patients with ischemic stroke versus 79 healthy controls were studied for the presence of ACE gene polymorphism detected by PCR. Genotypes were defined as DD, II and ID according to the presence of the D (deletion) and I (insertion) alleles. There was no statistically significant difference in either the genotypic distribution or allelic frequency between the patients versus healthy controls (chi2 = 0.105; df = 1; p = 0.430). There was also no significant difference for ACE genotype distribution and allelic frequency within the stroke group classified according to Bamford criteria (chi2 = 4.827; df = 3; p = 0.185). Our data supports lack of association between DD genotype and/or D allele and ischemic stroke or subtypes of ischaemic stroke in the Turkish population.     

The angiotensin-converting-enzyme insertion/deletion polymorphism is not related to venous thrombosis

The insertion/deletion (I/D) polymorphism of the gene for angiotensin-converting-enzyme (ACE) is associated with ACE plasma levels and activity. Conflicting results have been reported about the relevance of this polymorphism for venous thrombosis. The aim of the present study was to analyze the role of this polymorphism for deep venous thrombosis. The study was designed as a case-control study, including 330 patients with documented deep venous thrombosis and 354 controls. ACE genotype was determined by size-analysis of polymerase chain reaction products. Results showed that, ACE genotype frequencies were similar between patients (II: 24.8%; ID: 43.3%; DD: 31.8%) and controls (II: 22.9%; ID: 50.6%; DD: 26.6%, P = 0.15).The adjusted odds ratio of carriers of the DD geno-type for venous thrombosis was 1.24 (95% confidence interval 0.90-1.80).The polymorphism was furthermore not associated with age at first thromboembolic event or the occurrence of pulmonary embolism. From these results, we can conclude that the ACE I/D polymorphism is not a significant risk factor for deep venous thrombosis.     

Lack of an association between angiotensin-converting enzyme gene insertion/deletion polymorphism and ischaemic stroke

BACKGROUND AND PURPOSE: Numerous factors have been reported to influence the pathogenesis of stroke. The angiotensin I-converting enzyme (ACE) gene is a candidate gene for atherosclerotic-related diseases. In the present study, the association between the polymorphism of the ACE gene and ischaemic stroke was investigated. METHODS: Using polymerase chain reaction techniques, 100 patients (48 males, age 69.3 +/- 9.7 years) with cerebral infarction and 100 age- and sex-matched controls were divided into the following three ACE genotypes [deletion (D) and insertion (I)]: II, ID and DD. RESULTS: There was no evidence of any association between the ACE gene polymorphism and the presence of ischaemic stroke (odds ratio 0.874, 95% confidence interval 0.386-1.973). CONCLUSIONS: The DD genotype in the human ACE gene does not appear to be a risk factor for ischaemic stroke. Further evaluation in a larger population study is required to examine the possibility of an increased risk of ischaemic stroke in DD homozygotes.     

Angiotensin converting enzyme (I/D) gene polymorphism contributes to ischemic stroke risk in Caucasian individuals: a meta-analysis based on 22 case-control studies

Background: Stroke is a multifactorial disease in which genetic factors play an important role. Previous studies associated angiotensin converting enzyme (ACE) (insertion/deletion, I/D) gene polymorphism with ischemic stroke risk in Caucasian individuals reported conflicting results. The purpose of this study was to evaluate the association between ACE (I/D) gene polymorphism and ischemic stroke risk by a meta-analysis. Methods: The related studies were searched in MEDLINE, EMBASE and HuGEnet databases. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for ischemic stroke risk associated with this polymorphism were estimated using fixed-effect or random-effects model. Twenty-two studies (5528/5081 cases/controls) were eligible in our meta-analysis. Results: Overall, statistical associations of the ACE (I/D) polymorphism with ischemic stroke risk were found in dominant model (DD + ID versus II) : OR = 1.21, 95% CI = (1.06,1.38), P = 0.006, recessive model (DD versus ID + II): OR = 1.28, 95% CI = (1.05,1.55), P = 0.01, and homozygote comparison (DD versus II): OR = 1.37, 95% CI = (1.14,1.65), P = 0.001 for Caucasians. When stratifying according to stroke subtypes, there were similarly significant differences for small vessel disease in dominant model (DD + ID versus II) : OR = 1.44, 95% CI = (1.01,2.05), P = 0.04, recessive model (DD versus ID + II): OR = 1.30,95% CI = (1.09,1.55), P = 0.004, and homozygote comparison (DD versus II): OR = 1.44, 95% CI = (1.15,1.80), P = 0.001. Conclusion: This analysis suggests that the ACE (I/D) polymorphism may be a risk factor for ischemic stroke, genotype DD of ACE could increase the risk of ischemic stroke in Caucasians. Subgroup analyses indicate that stroke subtypes may be a genetic risk factor of ischemic stroke, and there might be a greater genetic liability with small vessel disease.     

Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii

OBJECTIVES: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. METHODS: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. RESULTS: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). CONCLUSIONS: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.     

血管紧张素转换酶基因多态性与中国人Binswanger病的关系

目的 探讨血管紧张素转换酶（ACE）基因多态性与中国人汉族Binswanger病（BD）及其危险因素的关系。方法 应用聚合酶链反应技术（PCR）测定111例中国汉族BD、98例高血压病患者和102名正常对照者ACE基因插入／缺失（I／D）多态性,用比色法测定血清ACE水平,调查BD孤危险因素及家族史。结果 BD组DD型基因频率为0．64,高于高血压病组的0．31（P＜0．01）和正常对照组的0．17（P＜0．01）,且D等位基因亦明显高于高血压病组和正常对照组（P＜0．01）。BD组中MRI所见轻（I）、中（Ⅱ）、重（Ⅲ）三度的DD型基因频率和D等位基因亦高于对照组（P＜0．01）。BD组血清ACE水平明显高于正常对照组（P＜0．01）。其中DD基因型血清ACE水平又高于同组DI基因和II基因（P＜0．01）。ACE基因型分布与BD患者的年龄、性别、体重指数、收缩压、舒张压、总胆固醇、甘油三脂等差异无显著性意义。结论 ACE基因缺失多态性可能是中国人汉族BD独立危险因素,循环ACE活性与基因缺失多态性相关。     

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke

Purpose: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke.

Method: This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR).

Result: In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = ?0.232, p = 0.024).

Conclusion: This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.     

The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction

Aims Heart rate variability (HRV) is a measure of cardiac autonomic control and is therefore subject to regulation by the renin-angiotensin system. The primary objective of this study was to determine the effect of an insertion/deletion polymorphism within the angiotensin-converting enzyme (ACE) gene on HRV in the early stages after a myocardial infarction at a time when cardiac autonomic control is deranged. The secondary objective was to determine whether this polymorphism affected the HRV response to inhibition of ACE. Major Findings 149 Caucasian subjects were studied 25 ± 16 h following MI using time and frequency domain measures of HRV derived from two 5-minute ECG recordings. Recordings were repeated at 182 ± 65 h following MI, when subjects had been stabilised on ramipril 2.5 mg bd. The study included 46 subjects with the DD genotype, 69 with the ID genotype, and 34 with the II genotype. No effect of the I/D polymorphism on short-term recordings of HRV was found. There was no difference in HRV response to the introduction of ramipril according to the genotypes. Principal Conclusions The I/D polymorphism within the ACE gene does not influence HRV after MI or the HRV response to ACE inhibitor therapy with ramipril. These findings may reflect the relative lack of importance of the I/D polymorphism and ACE activity in determining plasma and tissue angiotensin II concentration after a major stimulus to the renin-angiotensin system as occurs after myocardial infarction. Received: 6 November 2001, Accepted: 12 March 2002     

高血压性脑出血与血管紧张素转换酶基因多态性及血清水平关系的研究

目的：探讨原发性高血压（EH）,高血压性脑出血（CH）与血管紧张素转换酶（ACE）基因I／D多态性及血清ACE水平的相互关系。方法：对正常人（NC组）29例,EH组28例和CH组31例提取白细胞DNA,检测ACE基因型,等位基因和血清水平。结果：88例中不同ACE基因型血清ACE水平有显著性差异（DD＞ID＞II,P＜0．01）,EH组DD基因及D基因频率与NC组比较无显著性差异（P＜0．05）,CH组血清ACE水平和D基因频率显著高于NC组及EH组（P＜0．01）,其DD型的血清ACE水平也高于后二者（P＜0．05）,结论：ACE基因多态性及其血清水平与EH无关,而与CH呈正相关,D基因可能为高血压病患者脑出血发病的相对危险因素。     

Association between angiotensin I-converting enzyme insertion/deletion gene functional polymorphism and novelty seeking personality in healthy females

A certain type of personality is at risk for developing psychiatric diseases. Several lines of evidence support the interaction between brain angiotensins and central catecholamine systems, and suggest that angiotensin I-converting enzyme (ACE) may be a reasonable candidate gene for psychiatric disorders. The present study examined the possibility that ACE insertion (I)/deletion (D) functional polymorphism might be associated with particular personality traits. Healthy Japanese subjects (N=184) were administered the Temperament and Character Inventory (TCI) and the NEO Personality Inventory Revised version (NEO-PI-R), and their ACE I/D polymorphisms were determined. There was an ethnic difference in the genetic distribution of ACE I/D between Japanese (D=34.5%) and Caucasians (D=55.2%). We found that the scores of novelty seeking (NS) in the Low-ACE group (II genotype) of healthy female subjects were significantly lower than those in the High-ACE group (ID or DD genotype) (p=0.018). Our findings suggested that the ACE I/D polymorphism might be associated with the NS personality trait in females, but not males. Taking into account the effects of multiple comparisons, this result should be interpreted with caution, and needs confirmation in a larger sample.     

The DD genotype of the angiotensin converting enzyme gene independently associates with CMR-derived abnormal microvascular perfusion in patients with a first anterior ST-segment elevation myocardial infarction treated with thrombolytic agents

Introduction

The role of the angiotensin converting enzyme (ACE) gene on the result of thrombolysis at the microvascular level has not been addressed so far. We analyzed the implications of the insertion/deletion (I/D) polymorphism of the ACE gene on the presence of abnormal cardiovascular magnetic resonance (CMR)-derived microvascular perfusion after ST-segment elevation myocardial infarction (STEMI).

Materials and Methods

We studied 105 patients with a first anterior STEMI treated with thrombolytic agents and an open left anterior descending artery. Microvascular perfusion was assessed using first-pass perfusion CMR at 7 ±1 days. CMR studies were repeated 184 ± 11 days after STEMI. The ACE gene insertion/deletion (I/D) polymorphism was determined using polymerase chain reaction amplification.

Results

Overall genotype frequencies were II-ID 58% and DD 42%. Abnormal perfusion (≥ 1 segment) was detected in 56% of patients. The DD genotype associated to a higher risk of abnormal microvascular perfusion (68% vs. 47%, p = 0.03) and to a larger extent of perfusion deficit (median [percentile 25 - percentile 75]: 4 [0-6] vs. 0 [0-4] segments, p = 0.003). Once adjusted for baseline characteristics, the DD genotype independently increased the risk of abnormal microvascular perfusion (odds ratio [95% confidence intervals]: 2.5 [1.02-5.9], p = 0.04). Moreover, DD patients displayed a larger infarct size (35 ± 17 vs. 27 ± 15 g, p = 0.01) and a lower ejection fraction at 6 months (48 ± 14 vs. 54 ± 14%, p = 0.03).

Conclusions

The DD genotype associates to a higher risk of abnormal microvascular perfusion after STEMI.     

Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility

Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.     

Homozygous deletion genotype of angiotensin converting enzyme confers protection against migraine in man

Studies have shown that migraine may have a major genetic component. Meanwhile, angiotensin converting enzyme (ACE) gene has been implicated as a genetic factor associated with migraine. We designed a case-control study to investigate the association between ACE and migraine in 240 migraine patients and 200 healthy controls, matched by age and sex. There was no significant difference in allelic frequency (I and D) and genotype polymorphism (DD, DI and II) of the ACE gene in migraine patients and controls. Analysis of the difference in ACE polymorphism stratified by gender revealed that male migraine patients with the homozygote DD genotype (ACE-DD) were significantly fewer than that of male controls (OR = 0.331, p = 0.045). There was no existence of a difference among the frequency and duration of headache in each subgroup of migraine patients stratified by ACE genotype. Our findings indicate that ACE-DD may have a slight protective effect against migraine in male patients.     

Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes

OBJECTIVES: Pathological and clinical data suggest that patients presenting with ischaemic lacunar syndromes may be a heterogenous group. Those with isolated lacunar infarction are thought to have localised atherosclerosis whereas in those with coexisting leukoaraiois a distinct diffuse small vessel vasculopathy may be the predominant underlying pathology. The ACE insertion/deletion (I/D) polymorphism is an important candidate gene in ischaemic cerebrovascular disease but, where lacunar stroke specifically has been examined, there have been discrepant reports concerning a possible association. It was hypothesised that the influence of the ACE gene may be different among the two subgroups of ischaemic lacunar stroke reflecting the heterogeneity of the small vessel disease phenotype. METHODS: Eighty four consecutive patients presenting with classic lacunar syndromes were studied. All had acute cranial CT to exclude primary intracerebral haemorrhage and these were subsequently assessed for the presence and extent of leukoaraiosis. All patients were genotyped for the ACE insertion/deletion polymorphism. RESULTS: There was a significant difference in the distribution of ACE genotype with the DD genotype occurring more often in patients with leukoaraiosis and the II and ID genotypes occurring more often among those in whom this was absent (chi(2)=9.06, p=0.01). In a logistic regression model the ACE DD genotype remained as an independent predictor for the presence of leukoaraiosis (p=0.02) in patients presenting with classic lacunar syndromes. CONCLUSION: This study supports the hypothesis that there may be different types of small vessel disease in patients with classic lacunar syndromes and that the influence of the ACE DD genotype may be relevant in mediating the diffuse form of vessel injury.     

Angiotensin-converting enzyme insertion/deletion gene polymorphism in multiple sclerosis: a meta-analysis

The activity of angiotensin-converting enzyme (ACE) has been increased in the blood and cerebrospinal fluid of multiple sclerosis (MS) patients. In addition, there has been suppression of disease development in experimental autoimmune encephalomyelitis after blockade of ACE. These findings suggest that ACE may play a role in the MS pathogenesis. Since the previous studies investigating the association between the insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene and MS reported contradictory results, we performed a meta-analysis of four studies conducted in European populations of Slavic origin (1062 patients and 1067 controls) using the Comprehensive Meta-analysis 3.0 software. The results demonstrated that the ACE I/D polymorphism had no statistically significant association with an increased MS risk (all p ≥ 0.05) under all genetic comparison models: (1) allelic (D vs. I), (2) recessive (DD vs. ID + II), (3) dominant (DD + ID vs. II), and (4) additive (DD vs. ID vs. II). This meta-analysis indicates that the ACE I/D polymorphism is not associated with susceptibility to MS in Europeans of Slavic origin. Further studies with larger sample sizes from genetically different populations are warranted.     

Association study of angiotensin-converting enzyme gene polymorphism with schizophrenia and polydipsia.

Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system and can modulate dopamine turnover in the midbrain. Previous studies have revealed changes in the central ACE levels for schizophrenic patients, possibly related to the polydipsia commonly demonstrated for chronic schizophrenia. An insertion (I)/deletion (D) polymorphism of the ACE gene has been associated with ACE levels. Therefore, we elected to investigate the ACE I/D polymorphism for 124 schizophrenic patients and 117 control subjects. No significant differences for the genotype distribution or the allele frequency were revealed comparing controls and schizophrenic patients. The ACE genotypes were not associated with onset age or psychiatric symptoms for the schizophrenic cases. A modest association was revealed for this ACE polymorphism and polydipsia diagnosis for these patients. Using bearers of the D allele as baseline, the ratio for I/I homozygote was 2.31 (95% CI 0.95-5.65). This association needs further replication as it may have implications for the pathogenesis and the treatment of polydipsia for schizophrenic patients.