Angiotensin I Converting Enzyme Gene Polymorphism in Chinese Patients With Hypertension

Reports from different ethnic populations failed to show consistent findings on the association of hypertension with insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene. In this population association study in Chinese, we compared the distribution of the ACE genotypes and allele frequency in 150 healthy controls with normal blood pressure and 148 hypertensive patients categorized by age. Although the frequencies of homozygote deletion (DD) genotype and deletion allele were greater in Chinese with hypertension than in normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the differences were not significant by χ² analysis (P = .07 and .09, respectively). Furthermore, we did not find the trend of decreasing number of DD genotype in older hypertensive Chinese patients. The results indicated a much lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest association between I/D polymorphism of the ACE gene and hypertension in Chinese.     

Angiotensin converting enzyme gene polymorphism and activity in Turkish patients with essential hypertension

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with essential hypertension. We conducted a case-control study in Samsun, Turkey, to examine the association between ACE genotype, ACE serum activity, and blood pressure. Serum ACE activity was measured and ACE I/D polymorphism performed in 165 hypertensive and 143 normotensive subjects. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID, and II ACE genotypes was 65, 77, and 23 in hypertensive patients and 42, 82, and 19 in normotensive subjects (P > .05). The estimated frequency of the insertion allele was 0.37 in hypertensive and 0.42 in normotensive subjects. Nevertheless, sensitivity analysis, based on positive family history and severity of hypertension, suggested that significant associations existed between more homogeneous groups of hypertensives and normotensives (P < .05). ACE genotype influenced ACE activity and the highest level was in DD genotype, being the lowest in II genotype. ACE serum levels were significantly higher in hypertensives as compared with normotensives (P < .01). A modest correlation was observed between blood pressure and ACE among hypertensive persons (r = 0.25, P < .05) and this did persist in multivariate analysis (P < .05 for systolic blood pressure and P < .005 for diastolic blood pressure). These data suggest that ACE DD genotype may have predisposing effects on severe hypertensives and cases with positive family history, and that ACE may be one of the independent factors on hypertension.     

血管紧张素转化酶基因多态性对血清血管紧张素转化酶水平及血脂的影响

为探讨血管紧张素转化酶基因多态性对本地人群高血压患者和正常人血清血管紧张素转化酶及血脂水平的影响,采用聚合酶链反应技术,对118例高血压患者和98例正常人的血管紧张素转化酶基因插入/缺失多态性进行分型,并检测血清血管祭张素转化酶活性及血脂含量。结果发现,高血压组血管紧张素转化酶三种基因型(缺失纯合子型、插入纯合子型和杂合子型)及插入/缺失等位基因的频率与正常对照组比较差异无统计学意义(X2=0.468,P=0.791;X2=0.379,P=0.538)。血清血管紧张素转化酶活性在三种基因型之间差异有显著性意义(F=17.107,P=0.000)。高血压组总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)高于正常对照组(P<0.05);高血压组三种基因型之间血脂各指标含量及正常对照组三种基因型之间总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和载脂蛋白B含量差异有显著性意义(P<0.05)。此结果提示,血管紧张素转化酶基因多态性与血清血管肾张素转化酶活性及血脂含量有关,缺失纯合子型高血压患者血清血管紧张素转化酶活性最高且易患高脂血症。     

Angiotensin Converting Enzyme Gene Polymorphism in Turkish Asthmatic Patients

Asthma is a chronic inflammatory disease of the airways. Several candidate genes have been identified with a potential role in the pathogenesis of asthma, including the angiotensin converting enzyme (ACE) gene. We aimed to investigate the frequency of an ACE gene polymorphism in Turkish asthmatic patients and to determine its impact on clinical parameters and disease severity. Ninety-seven asthmatic patients (M/F 25/72, mean age 39 ± 13 years) and 96 healthy subjects (M/F 26/70, mean age 38 ± 12 years) were included. At baseline, all participants completed a questionnaire on demographics, symptoms, triggering factors, severity of asthma, and the presence of atopism. Blood samples were obtained from all patients and genomic DNA was isolated.

The frequency of the ACE genotypes (I = insertion and D = deletion) among asthmatics and controls were compared: asthmatics showed a 40.2% prevalence of the DD genotype (n = 39), ID was 45.4% (n = 44), and II was 14.4% (n = 14.4). In the control subjects, the frequency of DD was18.8% (n = 18), ID was 50% (n = 48) and II was 31.3% (n = 30). The DD ACEgenotype was significantly more frequent in asthmatics compared with controls (p < 0.001). Asthmatics with the ID ACE genotype showed a higher frequency of drug allergies, although this was not statistically significant (p = 0.08). Asthmatics with the DD genotype appeared to have a higher incidence of asthmatic episode exacerbations due to viral infections, but again this was not statistically significant (p = 0.08). Patients with mild or moderate-severe asthma had similar frequencies of these mutations.

We found a higher frequency of the ACE DD gene mutation in Turkish asthmatic patients compared with non-asthmatics, suggesting that this ACE gene polymorphism may be a risk factor for asthma but does not increase the severity of the disease.     

Deletion Polymorphism of Angiotensin-Converting Enzyme Gene and Left Ventricular Hypertrophy in Southern Italian Patients

Objectives. This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI).Background. The renin–angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy.Methods. The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient.Results. Left ventricular mass index values (mean ± SD) were 137 ± 28 g/m²in patients with the DD genotype, 125 ± 27 g/m²in those with the ID genotype and 115 ± 27 g/m²in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02).Conclusions. Our data show that the LVMI was significantly enhanced in patients with the DD genotype.(J Am Coll Cardiol 1997;29:365–9)     

Angiotensin converting enzyme genotype influences the response to the angiotensin II receptor antagonist losartan in patients with hypertension.

To examine whether the response to the angiotensin II receptor antagonist losartan varies depending on the angiotensin converting enzyme (ACE) genotype, we prospectively studied the effect of losartan in 42 hypertensive patients (20 men, 22 women; mean age: 60.4 years). After a 4-week observation period, losartan was administered at 50 mg/day and blood pressure was measured every 2 to 4 weeks for 12 weeks. Among the 42 patients, 19, 11, and 12, respectively, had the II, ID, and DD ACE genotypes. The baseline plasma ACE activity in patients with the ID or DD genotype was significantly higher than that in patients with the II genotype (13.8 +/- 4.2 vs. 9.6 +/- 2.3 IU/l; p = 0.0002). However, age, gender, baseline systolic and diastolic blood pressure (SBP/DBP), and body mass index (BMI) were not different among the groups. After 12 weeks of treatment with losartan alone, DBP in the ID+DD group was significantly higher than that in the II group (85.0 +/- 9.0 vs. 77.8 +/- 9.6 mmHg, p = 0.018), while the percent reduction in DBP in the ID+DD group was significantly smaller than that in the II group (7.9 +/- 8.8 vs. 14.3 +/- 10.1%, p = 0.035). Multiple regression analysis showed that the significant predictors of the DBP at 12 weeks were age (p = 0.030), ACE genotype (p = 0.029) and baseline DBP (p = 0.0001). The ACE genotype may be a determinant of the response to losartan in hypertensive patients.     

Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Associates with Increased Risk for Late Potentials in Patients with Myocardial Infarction

Background: The pathogenesis of the occurrence of late potentials (LP) has not been fully elucidated. Deletion polymorphism in the Angiotensin I-converting enzyme (ACE) gene may relate the myocarclial remodeling after the myocardial infarction (Ml). The purpose of this study was to evaluate the significance of ACE gene polymorphism for the occurrence of LPs after Ml. Methods: A 287 base pair (bp) insertion/deletion polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction and LPs were also examined by signal-averaged EGC in 136 patients with Ml. Polymorphism of the ACE gene was characterized by three genotypes: II, ID, and DD. Signal-averaged ECG were recorded using X, Y, Z leads and LP were defined by time-domain analysis as low amplitude potentials exceeding 20 ms after the QRS-end and filtered QRS >115 ms. Results: Positive LPs were noted in 40 of 136 patients with Ml. No differences could be detected between patients with LP-positive and LP-negative for the location of Ml, the success rate of reperfusion therapy, and left ventricular end-diastolic volume (126 ± 40 vs 113 ± 43 mL/m²). In patients with LP-positive compared with those in LP-negative, filtered QRS was significantly higher (135 ± 8 vs 107 ± 8 ms), left ventricular ejection fraction was lower (47 ± 12 vs 54%± 11 %), and peak was higher (3602 ± 2928 vs 2614 ± 2360 IU/L). The frequency of ACE/DD genotype was associated with patients with LP-positive (18 of DD, 18 of ID, and 4 of II for patients with LP-positive, while 25 of DD, 42 of ID, and 29 of II for patients with LP-negative). In the study population, the ACE / DD genotype was associated with patients with LP-positive when compared with the ACE ID & II genotype (x²= 4.7, P = 0.03). Conclusion: ACE/DD genotype of the ACE gene may be associated with the occurrence of LP after Ml.     

Predicting Response to Chronic Antihypertensive Treatment with Fosinopril: The Role of Angiotensin-Converting Enzyme Gene Polymorphism

Insertion (I)/deletion (D) polymorphism of the ACE gene has been reported to be involved in various cardiovascular diseases. We investigated prospectively whether the response to the ACE inhibitor fosinopril varied according to the ACE genotype in previously untreated Greek hypertensive patients. After a 4-week observation period, fosinopril was administered at a dose of 20 mg daily and blood pressure was measured weekly for 6 months. The study population consisted of 104 hypertensive patients (46 male, 58 female). There were no differences in age, gender, body mass index, and pretreatment blood pressure levels among patients with the DD, ID, and II genotypes (n = 42, 30, 32, respectively). The reduction in systolic blood pressure was significantly greater in patients carrying the DD compared to II or ID genotypes (5.6 ± 3.1 vs. 3.1 ± 1.1 or 3.6 ± 2.2, respectively; ANOVA, p < 0.05). The reduction in diastolic blood pressure was also significantly greater in DD hypertensives compared with II or ID (8.9 ± 6 vs. 5.5 ± 3.4 or 5.8 ± 4, respectively; ANOVA, p < 0.05). The age and BMI were not correlated with the changes in SBP or DBP that were observed after fosinopril administration. In conclusion, the ACE gene genotype was shown to influence the response to fosinopril in hypertensive patients.     

Angiotensin I-Converting Enzyme Gene Polymorphism and Acute Response to Captopril in Essential Hypertension

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be a determinant for serum ACE level and a marker for several cardiovascular diseases. We investigated whether the ACE gene can predict the therapeutic efficacy of ACE inhibitors in essential hypertensive patients. The response of blood pressure and plasma renin activity (PRA) 1 h after 50 mg captopril administration were evaluated in 82 inpatients with untreated essential hypertension (42 men, 40 women; mean age ± SD: 52 ± 13 years; range: 27 to 79 years) in relation to ACE genotypes. There were no differences in age, gender, blood pressure, and PRA in the basal conditions, among essential hypertensive patients with the II, ID, and DD genotypes (n = 36, 34, and 12, respectively). The acute responses of PRA and blood pressure to an ACE inhibitor were similar in the three groups. The blood pressure response was negatively correlated with baseline PRA (r = 0.497). These data suggest that PRA but not the I/D polymorphism of the ACE gene is a useful predictor of the short-term antihypertensive effects of ACE inhibitors.     

血管紧张素转换酶基因型与卡托普利疗效的相关性研究

目的 研究原发性高血压患者ACE基因多态性分布与卡托普利疗效的相关性。方法 133名原发性高血压患者按ACE基因多态性的II,ID与DD型三种,同时服用卡托普利25mg bid,服药前后作动态血压监测,以观察在各种不同ACE基因多态性间的区别。结果 ID患者在24小时收缩压,白天收缩压及夜间收缩压的降低程度均较其它型为明显（P＜0．05）。结论：转换酶抑制剂的作用可能与ACE的基因类型有关。     

Carotid thickening,cardiac hypertrophy,and angiotensin converting enzyme gene polymorphism in patients with hypertension

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been associated with increased risk for myocardial infarction, cardiomyopathy, carotid thickening, and cardiac hypertrophy. However, a conclusive agreement about the role of ACE genotype in the genetics of cardiovascular disease has not yet been reached. This study was undertaken to investigate the relationship of the I/D polymorphism of the ACE gene with carotid intima-media thickness (IMT) and left ventricular mass (LVM) in 175 Chinese patients with mild-to-moderate hypertension. The I/D genotypes were detected by the polymerase chain reaction using primers flanking the polymorphic region in intron 16 of the ACE gene. The IMT was measured in the common carotid and carotid bifurcation by B-mode ultrasound. The LVM was calculated with M-mode echocardiographic measures of the left ventricle. Patients with the DD genotype (n = 41) showed significant greater carotid IMT (1.593 ± 0.879 v1.309 ± 0.703 and 1.171 ± 0.583 mm, P = .01) but insignificant higher LVM index (123.8 ± 36.6 v 123.7 ± 37.4 and 118.2 ± 33.0 g/m², P = .61) than did those with the DI (n = 69) and II (n = 65) genotypes. The deletion polymorphism of the ACE gene (P = .04) was a significant predictor for carotid IMT on multiple regression analysis, controlling all the potential confounding factors including age (P = .001), systolic blood pressure (P = .09), smoking (P = .08), and plasma tissue plasminogen activator antigen (P = .03), but the LVM correlated only with age (P = .02), sex (P < .001), and body mass index (P < .001). These results indicated that the DD genotype of the ACE gene could be considered a risk factor for the development of early atherosclerosis in carotid arteries but not for left ventricular hypertrophy in the hypertensive population.     

Angiotensin Converting Enzyme Gene Polymorphism Is Not Related to Essential Hypertension in a Greek Population

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with essential hypertension. In addition, mistyping of the insertion allele in heterozygotes has been reported. We analyzed the ACE genotype of 98 hypertensive and 84 normotensive subjects of Greek origin. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. To avoid mistyping of heterozygotes, samples with the DD genotype were also amplified with primers that detect only the insertion allele. The distribution of the DD, ID, and II ACE genotypes was 30, 45, and 23 in hypertensive patients and 29, 40, and 15 in normotensive subjects, respectively. The estimated frequency of the insertion allele was 0.45 in hypertensive and 0.42 in normotensive subjects. The difference was not statistically significant. The results indicate a lack of association between ACE I/D polymorphism and essential hypertension in this Greek population, suggesting that other genes must contribute to the pathogenesis of hypertension. Am J Hypertens 1996; 9:700–702     

Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases: A study on North Indian patients

Angiotensin-converting enzyme (ACE) is the key enzyme of the renin angiotensin system (RAS) which maintains the blood pressure homeostasis in our body. The association of the ACE insertion/deletion (I/D) polymorphism with essential hypertension has been demonstrated by many studies. The purpose of the present study is to investigate the association of the insertion/deletion polymorphism of the ACE gene with hypertension and additive diseases in North Indian population. In total, 222 hypertensive and 218 normotensive adults participated in this hospital-based study. Anthropometric measures, lipids profiles, blood glucose, and blood pressure (BP) measures were collected from participants. ACE I/D polymorphism was determined by using insertion-specific amplification. The mean ages of study groups were 50.35 ± 12.40 and 47.32 ± 11.94 for cases and controls, respectively. Significant differences were observed in the frequencies of DD, ID, and II genotypes among the hypertensive and normotensive groups which were found to be 29.7%, 38.7%, and 31.5% vs. 53.7%, 23.4%, and 22.9%, respectively. It has been observed that the ACE ID genotype was significantly (p < 0.05) higher in hypertensive subjects, whereas, the DD genotype was significantly (p < 0.05) higher in control subjects. A strong association was found between cardiovascular diseases (CVDs) and ID genotype [p = 0.017, odds ratio (OR) = 3.091, 95% confidence interval (CI) = 1.224–7.807]. ID [p = 0.002, OR = 2.020, 95% CI = 1.281–3.185] and II [p = 0.032, OR = 1.677, 95% CI = 1.044–2.694] genotypes are more prone to diabetes with hypertension. This finding suggests that ACE insertion/deletion polymorphism is associated with hypertension and additive diseases in North Indians.     

Relationship between polymorphism of the angiotensin-converting enzyme gene and the response to angiotensin-converting enzyme inhibition in hypertensive patients.

The aim of this study was to investigate the relationship between polymorphism of the anglotensin-converting enzyme (ACE) gene and the blood pressure response to ACE inhibition in a hypertensive cohort. Imidapril (5-10 mg/day) or benazepril (10-20 mg/day) was administered for 6 weeks to 517 essential hypertensives. ACE gene polymorphism was examined by the polymerase chain reaction (PCR) method and the patients were classified as having the 190-bp deletion homozygous (DD) genotype, the 490-bp insertion homozygous (II) genotype, or the 490-bp insertion, 190-bp deletion heterozygous (ID) genotype. The achieved change in systolic and diastolic blood pressure (SBP and DBP) was analyzed for association with genotypes at the ACE gene locus. The DD genotype was observed in 132 patients (25.5%), the ID genotype in 255 patients (49.3%), and the II genotype in 130 patients (25.2%). The SBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -14.5 +/- 12.7 mmHg, -14.3 +/- 13.1 mmHg and -14.0 +/- 12.2 mmHg, respectively (p = 0.94). The DBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -8.7 +/- 7.4 mmHg, -8.7 +/- 7.7 mmHg and -8.5 +/- 6.7 mmHg, respectively (p = 0.96). There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition. These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition.     

血管紧张素转化酶和载脂蛋白E基因多态性对新诊2型糖尿病患者亚临床动脉粥样硬化的预测

目的 为探讨血管紧张素转化酶和载脂蛋白E基因多态性与新诊2型糖尿病多因素强化干预条件下亚临床动脉粥样硬化发生的关系。方法采用聚合酶链反应一限制性片段长度多态性方法检测湖南地区汉族新诊2型糖尿病患者及93例无糖尿病对照者血管紧张素转化酶及载脂蛋白E的基因多态性，分别比较血管紧张素转化酶和载脂蛋白E基因型间以及两基因型协同作用下体重、血糖、血压、血脂和胰岛素抵抗等代谢指标水平的差异，比较分析无动脉粥样硬化与亚临床动脉粥样硬化患者血管紧张素转化酶及载脂蛋白E基因型分布特点。采用Logistie回归模型分析血管紧张素转化酶、载脂蛋白E基因型及二者协同作用下与多因素干预条件下亚临床动脉粥样硬化发生的关系。结果157例新诊2型糖尿病患者中，载脂蛋白E基因型及等位基因频率分布与对照组比较差异无显著性（P〉0．05）；血管紧张素转化酶Ⅰ等位基因频率显著高于对照组（0．707比0．581，P〈0．05），血管紧张素转化酶DD携带者收缩压水平与Ⅱ及ID携带者比较差异无显著性（P〉0．05）。载脂蛋白E4IX基因型携带者低密度脂蛋白胆固醇水平显著高于2/X携带者（P〈0．01）；血管紧张素转化酶及载脂蛋白E基因型对收缩压及低密度脂蛋白胆固醇水平无交互作用。两基因多态性与各代谢指标干预1年达标情况和动脉内中膜厚度无相关关系（P〉0．05）。血管紧张素转化酶DD携带者无一例发生亚临床动脉粥样硬化，与非DD携带者比较差异接近显著性（P=0．059），未发现载脂蛋白E基因多态性与亚临床动脉粥样硬化发生的相关性。结论以上提示，载脂蛋白E基因多态性对新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化的发生无预测作用；血管紧张素转化酶DD基因型可能是新诊2型糖尿病患者多因素干预条件下亚临床动脉粥样硬化发生的负性预测因子。     

Distribution of different HLA antigens in Greek hypertensives according to the angiotensin-converting enzyme genotype

The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is an independent risk factor for cardiovascular disease. It has also been suggested that some HLA genes may contribute to the genetic susceptibility to essential hypertension. So far, an association between ACE polymorphism and HLA antigens in arterial hypertension has not been reported. We have studied 94 subjects with newly diagnosed essential hypertension, 49 men and 45 women (mean age, 52.3 ± 11.3 years), as well as 104 randomly selected, age- and gender-matched normotensive individuals (54 men and 50 women, mean age 48.7 ± 10.8 years). Both cohorts originated from the Greek population and lived in the greater Athens area. The ACE genotype was analyzed by polymerase chain reaction. HLA class I and II antigens were studied by serologic and molecular techniques.The prevalence of the ACE genotypes did not differ significantly between hypertensives and normal individuals. The casual blood pressure levels and the average ambulatory blood pressure levels were similar among the three ACE genotypes. Hypertensives with the ACE-DD genotype were characterized by an increased prevalence of the HLA-A2 antigen (50% v 31.4%, P < .005) and DR6 (16.7% v 11.4%, P < .01) in comparison to the normotensive subjects with the ACE-DD genotype. HLA-A24 was found more frequently among the hypertensives with the ACE-ID genotype than in the normal controls with the same genotype (35.5% v 26.4%, P < .05). ACE-DD genotype is associated with a high prevalence of specific HLA antigens. The coexistence of the ACE-DD genotype with certain HLA phenotypes could reveal a distinct hypertensive population with increased risk for cardiovascular events.     

Lack of association of the angiotensin converting enzyme gene polymorphism with essential hypertension in a chinese population

To examine the association between insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and essential hypertension in a Chinese population, a case-control study was conducted using 157 hypertensive and 115 normotensive subjects. The I/D polymorphism of the ACE gene was identified by polymerase chain reaction. Plasma ACE activity was determined using spectrophotometry. The difference of allele frequencies between normotensives and hypertensives was statistically significant (X² = 4.467, P = .035), while the gentotype distribution was not different between normotensive and hypertensive subjects (X² = 3.954, P = .138). Plasma ACE activity was highest in the DD genotype, followed by the ID genotype, and the lowest in the II genotype (P = .0001 in normotensives and P = .163 in hypertensives, respectively). Thus, we conclude that the ACE gene polymorphism is not associated with essential hypertension in this Chinese population, but plasma ACE activity is genetically determined in the normotensive Chinese.     

Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.     

Impact of α- Versus β-Blockers on Hypertensive Target Organ Damage: Results of a Double-Blind,Randomized, Controlled Clinical Trial

In hypertensive disease, the extent of target organ damage determines the prognosis. We conducted a 6-month, double-blind randomized study to compare the effects of an α₁-adrenoreceptor blocker (bunazosin) with those of a β₁-adrenoreceptor blocker (metoprolol) on early hypertensive target organ damage at a similar level of blood pressure reduction. The study consisted of 43 patients (29 men and 14 women) of varying ages (mean age 52 ± 9 years) with essential hypertension World Health Organization stage I–II. Both the α- and the β-blocker lowered blood pressure to a similar extent measured by 24-h blood pressure monitoring. The left ventricular mass was comparably reduced in both cohorts (α-blocker 284 ± 80 v 259 ± 67 g, P < .05, β-blocker 282 ± 74 v 254 ± 70 g, P < .05). Treatment with the α-blocker led to reduced total peripheral resistance (22.9 ± 8.0 v 19.9 ± 5.3 U, P < .05), whereas therapy with the β-blocker resulted in an elevated total peripheral resistance (25.5 ± 8.4 v 28.5 ± 9.3 U, P < .10; P < .05 for the difference in both groups). Renal plasma flow remained constant in the α-blocker treated group but decreased in the β-blocker treated group (508 ± 141 v 477 ± 134 mL/min/1.73 m², P < .05). Glomerular filtration rate as measured by inulin clearance tended to increase after treatment with the α-blocker (112 ± 20 v 115 ± 18 mL/min/1.73 m², P < .10) in accordance with a decrease of serum creatinine (1.00 ± 0.14 v 0.93 ± 0.12 mg/dL, P < .001). Plasma cholesterol and LDL cholesterol was lowered after treatment with the α-blocker (238 ± 48 v 312 ± 37 mg/dL; P < .001, and 153 ± 32 v 130 ± 25 mg/dL; P < .05) while remaining unchanged in group treated with the β-blocker. Left ventricular hypertrophy was similarily reduced with α- and with β-blockade at a comparable reduction of 24-h blood pressure. α-Blockers effected a more favorable renal and systemic hemodynamic profile than β-blockers, but only long-term prospective studies will answer the question whether these hemodynamic effects result into a better cardiovascular prognosis.     

Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated With Coronary Artery Plaque Calcification As Assessed by Intravascular Ultrasound

Objectives. We evaluated the influence of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque morphology and calcification in patients with angiographically documented coronary artery disease (CAD).Background. The ACE I/D polymorphism has been associated with an increased risk of myocardial infarction in patients with the DD genotype but not with the presence of native CAD.Methods. We studied 146 patients undergoing percutaneous transluminal coronary angioplasty for stable angina pectoris by means of preinterventional intravascular ultrasound (IVUS). Qualitative and quantitative criteria were used to classify the target lesions as poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion-specific PCR in DD genotypes to prevent mistyping.Results. The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the basic characteristics. Patients with the DD genotype had significantly more calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95% confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180° of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05 to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31).Conclusions. Patients with CAD and the ACE DD genotype have a significantly higher incidence and greater extent of coronary lesion calcification, as determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is related to the development or progression of atherosclerotic plaque calcification.