Genotype Of Angiotensin-converting Enzyme Gene Research Articles

The Effects of the ACE Gene Insertion/Deletion Polymorphism on Glucose Tolerance and Insulin Secretion in Elderly People Are Modified by Birth Weight

The I allele of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) appears to be protective against the complications of type 2 diabetes. Low birth weight, a marker of an adverse intrauterine environment, is associated with higher rates of type 2 diabetes. We examined whether the ACE I/D polymorphism could explain or modify the association between low birth weight and adulthood glucose tolerance. We measured plasma glucose and insulin concentrations after an oral glucose challenge in a group of 423 men and women, ages 65-75 yr, with measurements at birth recorded. The presence of the I allele was associated with shorter duration of gestation (P = 0.006) and, relative to gestational age, higher birth weight (P = 0.008) and length (P = 0.02). The I allele was associated with lower glucose at 120 min (P = 0.04) and a greater insulin response (P = 0.03 for insulin at 30 min and P = 0.06 for insulin area under the curve) to a standard oral glucose tolerance test. However, the associations between the ACE genotype and adulthood insulin secretion were only present in people with low birth weight (P for interaction birth weight * ACE genotype on insulin at 30 min = 0.003 and on insulin area under the curve = 0.05). The ACE I allele is associated with shorter duration of gestation and higher birth weight. The association between the presence of the ACE I allele and increased indices of adult insulin secretion is confined to subjects with low birth weight. We suggest that these findings reflect interactions between genotype and intrauterine environment with resulting changes in gene expression.

Angiotensin-converting enzyme, sleep-disordered breathing, and hypertension.

The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism influences ACE activity, cardiovascular risk, blood pressure, and possibly the risk of developing Alzheimer's dementia. We explored the association of the insertion/deletion polymorphism with sleep-disordered breathing (SDB) and hypertension in 1,100 subjects of the Wisconsin Sleep Cohort. The polymorphism did not influence body mass index or the occurrence of SDB, but was dose-dependently associated with blood pressure. Interestingly, SDB and the insertion/deletion polymorphism interacted significantly to modulate blood pressure independently of age, sex, ethnicity, and body mass index. Most specifically, the association of the deletion allele with hypertension was most pronounced in subjects with mild to moderate degrees of sleep apnea (5 < or = apnea-hypopnea index < or = 30). We hypothesize that in the absence of SDB the effect of the deletion allele alone may not be sufficient to increase blood pressure. At severe levels of SDB, the effect of sleep apnea on blood pressure overwhelms any association of the deletion allele with hypertension and occurs independent of any ACE gene genotype.

Angiotensin-converting enzyme and p22 phox polymorphisms and the risk of coronary heart disease in a low-risk Spanish population

Objective: To evaluate the genetic contribution to myocardial infarction in a homogeneous Caucasian population (a Mediterranean Spanish population) with very low frequency of coronary heart disease (CHD). Design: We analyzed a total of 210 subjects, younger than 55 years, considered to be a low-risk population (104 cases of myocardial infarction and 106 control), and genotyped them (using polymerase chain reaction and sequencing) for the angiotensin-converting enzyme (ACE) insertion/deletion (ACE I/D) and for the C242T polymorphism of NADPH oxidase p22 phox. Also, we sequenced 23 alleles of the ACE gene (9 D and 14 I) for the region that includes the end of the intron 16 and the exon 17. Results: The ACE genotype-prevalence values for II, ID and DD were 4.81%, 28.85% and 66.34%, respectively, among the myocardial infarction patients, and 2.83%, 71.70% and 25.47% among controls. The statistical analysis comparing patients and controls revealed significant differences ( χ 2=25.09, P=0.00000055) between the two subpopulations. Also, we found a strong association between the genotype DD and the risk of suffering CHD (odds ratio (OR): 3.64; 95% CI: 2.37–8.07). The prevalence of the CC, TC and TT genotypes of p22 phox gene among healthy controls proved to be 53.77%, 44.34% and 1.89%, while those of myocardial infarction were 58.65%, 39.42% and 1.93%, respectively. The association of C242T polymorphism of the p22 phox gene with CHD was not statistically significant, ( χ 2=0.49, P=0.48). Logistic-regression analysis demonstrated that the independent risk factor for developing myocardial infarction was the DD genotype of ACE gene. Finally, our results indicate that alleles I and D of ACE gene are differentiated at three positions (nucleotide sites 14,480, 14,488 and 14,521) of which, the positions 14,480 and 14,488 were in absolute linkage disequilibrium. Conclusions: Among subjects of a Mediterranean population with low risk for CHD, the presence of DD ACE genotype could be a risk factor for myocardial infarction, and we confirm the linkage disequilibrium between two nucleotide positions of the ACE gene and the polymorphism for an Alu insertion.

Correlation of angiotensin-converting enzyme(ACE) gene insertion/deletion polymorphism with prethrombotic state and essential hypertension

目的 探讨血管紧张素转换酶(ACE)基因I/D多态性与原发性高血压(EH)及高血压血栓前状态(PTS)的关系.方法 PCR检测61例原发性高血压病人和正常对照组28例的ACE基因I/D多态性;发色底物法测t-PA、PAI-1活性,酶联免疫吸附双抗夹心法(ELISA)测vWF含量.结果高血压组DD基因型频率显著高于对照组(P＜0.05),但D等位基因频率分布在高血压组和正常组之间差异无显著意义(P＞0.05).高血压组t-PA活性降低,PAI-1活性、vWF含量升高(P均＜0.001).高血压组DD型t-P活性明显低于ID、II型(P＜0.001),而ID、II型之间差异无显著意义(P＞0.05),DD型PAI-1活性明显高于ID、II型(P＜0.001),而ID、II型之间差异无显著意义(P＞0.05),vWF在DD、ID、II型三者之间差异无显著意义(P＞0.05).结论 DD型是原发性高血压发病的危险因素.原发性高血压存在血栓前状态.t-PA、PAI-1的变化与血管紧张素转换酶基因I/D多态性有关,DD基因型可引起血栓前状态。

II genotype of the angiotensin-converting enzyme gene increases the risk for subarachnoid hemorrhage from ruptured aneurysm.

Evidence exists in support of a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (SAH) in humans. Meta-analysis of 2 previous studies showed that the I allele of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism was a weak, but significant, risk factor for aneurysmal SAH. Moreover, a recent study has shown that the local renin-angiotensin system (RAS) is involved in the development of intracranial aneurysm. The aim of this study was to investigate the association between ACE I/D polymorphism and a risk for aneurysmal SAH in a Polish population. Ninety patients with aneurysmal SAH (mean age: 48.9+/-14.0 years) and 128 healthy controls matched for age and sex were genotyped for the ACE I/D polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography and/or lumbar puncture and digital subtraction angiography. ACE gene polymorphism was detected by polymerase chain reaction amplification of the intron 16-specific I/D fragments, 490-bp and 190-bp, respectively. The ACE genotype distribution in patients with aneurysmal SAH (II, 52.2%; ID, 15.6%; DD, 32.2%) differed significantly from controls (II, 23.4%; ID, 50.8%; DD, 25.8%) (P<0.001). A logistic regression model showed that the II genotype of ACE gene was independent from female sex and smoking as a risk factor for aneurysmal SAH (OR, 4.57; 95% CI, 2.35 to 8.90). Here we report that II genotype of ACE gene is a risk factor for aneurysmal SAH.

Association of angiotensin converting enzyme gene I/D polymorphism of vitiligo in Korean population.

Vitiligo (leukoderma) is an acquired idiopathic hypomelanotic disorder characterized by the circumscribed depigmented patches. Vitiligo is a polygenic disease. The exact pathogenesis is not yet known. The angiotensin converting enzyme (ACE) gene was selected as a candidate gene as ACE plays an important role in the physiology of the vasculature, blood pressure and inflammation, and its relationship with various diseases, including autoimmune diseases, has been widely investigated. The I/D polymorphism of ACE gene in vitiligo patients has not been reported. In this study, we investigated ACE gene polymorphism in 120 vitiligo patients and in 429 healthy volunteers in Korea. The ACE gene genotype distribution (P = 0.032) and allele frequency (P = 0.012) were significantly different between vitiligo patients and healthy controls. This study suggests that the ACE gene polymorphism has a strong association with the development of vitiligo in Korean patients.

Angiotensin-converting enzyme insertion/deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin.

The aim of this study was to assess the relationship between the angiotensin converting enzyme gene (ACE) genotype and endothelium-dependent coronary vasomotor and fibrinolytic activity. The ACE DD genotype has been reported to be a risk factor for myocardial infarction. However, the mechanism is unknown. The fibrinolytic and renin-angiotensin systems are linked via ACE at the vascular beds. We studied 73 patients (II: n=24; ID: n=37; DD: n=12) who underwent diagnostic cardiac catheterization. Graded doses of bradykinin (BK) (0.2, 0.6, 2.0 microg/min) and acetylcholine (30,100 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). Coronary release of tPA antigen was determined as a CS-Ao gradientXCBFX[(100-hematocrit) / 100]. ACE genotypes were determined using polymerase chain reaction. The ACE genotype did not appear to affect coronary macro- and microvascular responses induced by BK or acetylcholine. Coronary tissue plasminogen activator (tPA) release induced by BK was depressed in subjects with the ACE DD genotype. ACE levels in the DD genotype were significantly higher than those in the ID or II genotype. In all of the subjects, there was a significant negative correlation between the serum level of ACE activity and net coronary tPA release in response to BK at 0.6 microg/min. In conclusions, the DD genotype of the ACE gene impairs the coronary release of tPA induced by BK.

Angiotensin-converting enzyme gene polymorphism may influence blood loss in a geriatric population undergoing total hip arthroplasty.

To evaluate how angiotensin-converting enzyme (ACE) gene polymorphism is associated with perioperative blood loss in hip arthroplasty in a geriatric population. A case-control study of subjects consecutively undergoing total hip arthroplasty. A department of orthopedic surgery in Italy. One hundred five patients, mean age +/- standard deviation 68.6 +/- 10.4, undergoing total hip arthroplasty. ACE gene polymorphism was analyzed using polymerase chain reaction. Decrement of hemoglobin (Hb) and hematocrit (Ht) was calculated as the difference between the preoperative and the lowest postoperative value, measured 1, 2, and 3 days after surgery. Total blood loss was calculated as the sum of intra- and postoperative blood loss. Patients carrying the deletion homozygous and insertion/deletion heterozygous genotypes of the ACE gene show a higher decrement of Hb (P <.01) and Ht (P <.01) and higher total blood loss (P <.007) after hip surgery than subjects carrying the insertion (II) homozygous. The role of ACE gene polymorphism seems hypertension independent. Logistic regression analysis showed that II genotype reduces total blood loss. This is the largest study evaluating the distribution of ACE gene genotypes in patients undergoing hip arthroplasty and the first investigating the association between bleeding and ACE gene polymorphism. Our data suggest that II genotype is associated with lower total blood loss.

Angiotensin-converting enzyme gene polymorphism in patients with Essential hypertension

Several genetic investigations have been attempted to elucidate the association of angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension. This study was conducted to investigate the frequency of ACE gene insertion/deletion (I/D) polymorphism in patients with essential hypertension (EH). The study included one hundred patients with essential hypertension and seventy age and sex matched healthy individuals as a control group. The patients and control group were subjected to routine investigations, assay of serum cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and assay of ACE gene I/D polymorphism using real-time polymerase chain reaction (PCR). The results of the study showed that the frequency of DD,ID and II genotypes were 42%, 44% and 14 % respectively in hypertensive group and 30%, 50% and 14 % respectively in control group with significantly higher frequency of DD genotype in patients as compared to the control group (p<0.05). There was a significant association between DD genotype and hypertension, as there was significant increase in both systolic and diastolic blood pressure in patients with DD genotype as compared to other genotypes. Serum cholesterol , HDL-C and LDL –C levels showed significant increase in patients as compared to the control group (P <0.001, P <0.001 and P <0.001: respectively ) Also, serum Cholesterol and LDL-C levels showed significant increase in patients with DD and ID genotypes as compared to II genotype , while triglycerides and HDL-C didn’t show differences between the three genotypes. It was concluded that the DD genotype of ACE gene showed significantly higher frequency among patients with essential hypertension as compared to the normal subjects and that DD genotype was associated with significantly higher blood pressure as compared to ID and II genotypes. Also, DD genotype was associated with significantly higher serum cholesterol and LDL-C as compared to II genotype. This polymorphism in the ACE gene may contribute to the pathogenesis and severity of essential hypertension and may help in selection of anti-hypertensive drugs.

Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE.

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.

Real-time PCR for rapid genotyping of angiotensin-converting enzyme insertion/deletion polymorphism

Objective: To develop a real-time PCR technique for detection of the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene. Design and methods: Three primers were designed for performing real-time PCR in the presence of SYBR Green I as flurochrome followed by melting curve analysis. Forty human genomic DNA that have been genotyped by two-rounds of conventional PCR were used for evaluation of this technique. Results: Melting curve analysis indicated the melting peak at 73.9°C and 76.2°C corresponding to the presence of I and D alleles, respectively. Comparable genotyping results were obtained by both conventional and real-time PCR. Besides, the mistyping of ID allele individuals by the first run of conventional PCR were accurately genotyped by single-tube real time PCR. Conclusions: The real-time PCR method presented in this study provides a rapid and sensitive way for genotyping of ACE gene that may be suitable for large-scale clinical and epidemiologic study.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension

Background Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. Methods The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D -dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). Results Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =.012), tPA antigen (P =.0001), fibrinogen (P =.0002), D -dimer (P =.0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. Conclusions Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension. (Am Heart J 2000;140:760-5.)

A role of angiotensin-converting enzyme gene polymorphism in left ventricular remodeling after myocardial infarction.

Left ventricular remodeling (LVR) process is one of the important secondary sequele after acute myocardial infarction (AMI). However, little is known about the relationship between LVR and angiotensin converting enzyme (ACE) gene polymorphism as well as endothelial nitric oxide synthase (ecNOS) gene polymorphism. Coronary angiography and left ventriculography were performed within 24 hours and 30+/-7 days after AMI onset. All consecutive 24 patients (57+/-6 years) had acute anterior MI with one vessel disease of left anterior descending artery and successful revascularization therapy during acute phase. Patients were divided into three groups according to the change of end-diastolic volume index (EDVI)(Delta EDVI = EDVI 1 month-EDVI within 24 hrs); LVR(+) (Delta EDVI>7.0 ml/m(2), n = 5), LVR (-)(Delta EDVI<-7.0 ml/m(2), n = 13), and LVR (+/-)(-7.0<Delta EDVI<7.0 ml/m(2), n = 6) groups. The polymorphisms of ACE and ecNOS gene were determined with PCR method after an extraction of genomic DNA from peripheral leukocytes. There were no significant difference among three groups as to baseline characteristics, including coronary risk factors, medications, serum CPKmax and patency of infarct-related artery. The incidence of DD genotype of ACE gene is significantly higher in LVR (+) than in the other two groups (0.60; 0; 0, respectively, chi(2) = 13.150, p<0.01). The incidence of D allele of ACE gene is also significantly higher in LVR (+) than in the other two groups (0.70; 0.17; 0.19, respectively, chi(2) = 10.221, p<0.01). Delta EDVI of DD genotype was significantly greater than in the other two groups (DD genotype = 30.1+/-18.1; ID genotype = -13.0+/-27.4; II genotype = -8.2+/-11.5 ml/m(2), respectively, p<0.05). There was no significant difference in ecNOS gene polymorphism among three groups. By stepwise regression analysis, the significant independent predictors of Delta EDVI were EDVI within 24 hrs and DD genotype (F = 16.88 and 8.641, respectively, p = 0.0024). These results showed that left ventricular dilatation is related to DD genotype of ACE gene after successful reperfusion therapy of anterior AMI. Thus, renin-angiotensin system may play an important role in left ventricular remodeling after AMI.

Synergistic effect of angiotensin-converting enzyme and angiotensinogen gene on cardiac hypertrophy

Aims: There are controversies concerning the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH), and the unclear association between angiotensinogen (ATG) M235T polymorphism and LVH. We investigated both the separate and interactive effects of these two genes on LVH in patients ( N=396) with cardiovascular disease and normal healthy volunteers ( N=133). Results: Frequency of DD genotype of ACE gene was significantly ( P<0.05) higher in patients with LVH than patients without LVH or normal controls. Frequency of TT genotype of ATG gene in patients with LVH was significantly ( P<0.01) greater than that in normal controls or marginally ( P=0.1) higher than that in patients without LVH. These findings were also observed in normotensive patients and normal controls after excluding hypertensive patients. Only in patient group, the frequency of DD genotype in the highest quartile of LVMI was significantly greater than that in the lowest quartile ( P<0.05). The higher tendency of TT genotype in the highest quartile patients compared with that in the lowest, did not reach statistical significance. In combined genotype analysis, there was a remarkable difference in LVMI between the two extreme double homozygotes only in patient group (156±25 versus 109±25 g/m 2 for TT+DD versus MM+II) ( P<0.01). In ANCOVA, the interaction term composed of ACE and ATG genotype was a significant independent variable for LVMI only in the male patient group ( P<0.01). Conclusion: The D-allele of ACE and T-allele of ATG gene exert a synergistic effect on cardiac hypertrophy in male patients with cardiovascular diseases, but not in normal healthy population.

Variant angina is not associated with angiotensin I converting enzyme gene polymorphism but rather with smoking.

Angiotensin converting enzyme (ACE) perhaps plays roles in regulating coronary vasomotor tone by producing angiotensin II and degrading bradykinin. We sought to investigate the role of ACE gene polymorphism in the pathogenesis of variant angina and to compare it with that of other clinical risk factors for male patients with variant angina and age-matched and sex-matched control subjects. We studied 78 male patients with variant angina who exhibited spontaneous or provoked coronary spasms during coronary angiography and compared prevalences of ACE gene genotype (deletion D and insertion I) and other risk factors between this group of patients with variant angina and age-matched and sex-matched control subjects whose angiograms were normal and in whom the ergonovine test did not cause spasms (n = 80). Smokers were more prevalent in the group of patients with variant angina (P < 0.05). Genotype and allele prevalences of the group of patients with variant angina (0.14, 0.53 and 0.33 for DD, DI and II and 0.41 and 0.59 for D and I, respectively) were no different from those of the control group (0.16, 0.49 and 0.35 for DD, DI and II and 0.40 and 0.60 for D and I). Multiple logistic regression analysis showed that smoking was a significant risk factor for variant angina (odds ratio 2.61, 95% confidence interval 1.03-6.66) whereas ACE genotype was not. Variant angina is associated with an environmental factor, such as smoking, rather than a genetic factor, such as ACE gene polymorphism.

Angiotensin-converting enzyme gene polymorphism and reversibility of uremic left ventricular hypertrophy following long-term antihypertensive therapy

Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. Thirteen DD and 17 II + ID hemodialyzed uremics were followed-up with yearly echocardiography and 24-hour blood pressure (BP) monitoring over five years while on an antihypertensive therapy that included ACE inhibitors as first line drugs. In the II + ID group there were significant decreases of the left ventricular mass index (LVMi) and of both systolic and diastolic BPs. These changes were less pronounced in the DD group, but the difference was not statistically significant given the wide overlap between the two groups. Further analysis of the data revealed that the only factor associated to a decreased LVMi was the decrease of the systolic BP irrespective of the ACE gene genotype of each individual patient. The ACE-gene genotype does not necessarily predict the extent to which LVMi will be lowered by ACE-inhibitors therapy. The LVH of hypertensive uremics is amenable by long-term antihypertensive therapy provided that it results in significantly decreased systolic blood pressure.

Is ACE gene polymorphism associated with lone atrial fibrillation?

ACE (angiotensin converting enzyme) gene genotypes have been shown to be a risk factor for development of left ventricular hypertrophy and cardiomyopathy, upon the assumption that the DD genotype is linked to higher cellular ACE activity leading to myocardial fibrosis. To test an analogous hypothesis that the DD genotype favors myocardial fibrosis in the atrium and thus promotes atrial fibrillation without any structural heart diseases, we determined the distribution of the ACE gene genotypes in 77 patients with lone atrial fibrillation and investigated the effects of the ACE genotypes on the clinical characteristics of atrial fibrillation. The distribution of ACE genotypes was not significantly different between the patients and healthy volunteers. Also, the ACE gene genotypes did not affect the types of atrial fibrillation and the age at the onset of atrial fibrillation. Thus, these results refuted the hypothesis of possible relationships between ACE genotypes and lone atrial fibrillation through myocardial fibrosis, and indicated some unknown differences between the atrium and ventricle.

Association of ACE gene polymorphisms with coronary artery disease in a northern area of Japan.

The insertion/deletion DNA polymorphism of the gene coding human angiotensin converting enzyme (ACE) was examined in 109 patients with coronary artery disease (CAD) and 93 non-coronary subjects (NCS) living in a northern part of Japan. The presence of risk factors including age, hypertension, hypercholesterolemia, tobacco use, diabetes mellitus and hyperuricemia were also examined. An insertion (I) / deletion (D) polymorphism of the ACE gene was determined by the polymerase chain reaction with oligonucleotide primers encompassing the polymorphic region in intron 16. The template DNA was isolated from peripheral blood leukocytes of patients. The frequency of the D-allele in NCS was 0.27, significantly lower than that reported in Caucasians or in Japanese living in the Osaka area. The frequency of the D-allele in patients with myocardial infarction (MI) and angina pectoris was 0.39 and was higher than that in NCS. The frequencies of genotypes DD, ID, and II were 17.8, 43.3 and 38.9%, respectively, in CAD except in young patients (below 40 years of age) with MI and AP groups, and 6.5, 40.9 and 52.7%, respectively in NCS (p < 0.05 between CAD and NCS). Young MI showed similar frequencies in ACE gene polymorphisms to those in NCS, a pattern which differed from that seen in subjects with CAD (p < 0.05). The numbers of risk factors did not alter the frequency of ACE gene genotype among patients with CAD, however, in normotensives, the odds ratio of DD-genotype was significantly increased to 3.4. Accordingly, ACE gene polymorphism may be associated with morbidity from CAD in Japanese living in northern Japan as has been noted in Caucasians, despite the lower frequencies of the D-allele in the Japanese population.