Angiotensin-converting Enzyme Genotype Research Articles

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study

BackgroundThe role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. MethodsThis single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. ResultsThe II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI=0.114–0.558; p=0.007), for that of II genotype was 1.93 (95% CI=0.86–4.3; p=0.107) and for DD genotype was 7.225 (95% CI; 1.88–27.6; p=0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds=4.25; 95% CI=2.01–6.7; p=0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. ConclusionACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.

Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study.

Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia. We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals. 178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited. Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE). The DD genotype for ACE was independently associated ( b = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07). Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia.

A New Investigative Approach: How the Angiotensin-Converting Enzyme Gene Interacts with Coronary Risk Factors

How each Angiotensin-Converting Enzyme (ACE) genotype modulates the magnitude of the effect of each coronary risk factor. Background: Coronary Artery Disease (CAD) is based on atherosclerosis, which is a multifactorial-multigenic disease. This study investigated when interacting with them in the genesis of this pathology. Methods: The study included 630 subjects, including one group with 396 CAD-confirmed patients and another with 234 controls without angiographic lesions. Classical risk factors of CAD and ACE gene polymorphisms were evaluated using nested PCR. The association between the DD, ID and II genotypes with classical risk factors was analysed statistically by comparing the patient and control groups using the binomial frequency comparison test and the power test. Results: Of the 630 individuals, 286 presented the DD genotype, and there were 251 ID genotypes and 93 II genotypes. In the comparative analysis of the genotype frequencies between the patient and control groups, the DD genotype showed the most significant difference and the highest power (p=0.0020; power=0.8454). In the analysis of the interaction between risk factors and the ACE genotype in the DD genotype, a significant difference and a high power in the family history of CAD (p=0.0043; power=0.08355); (p=0.0010; power=0.9155), high total cholesterol levels (p<0.0001; power=0.9983) and high LDL cholesterol levels (p=0.0004; power=0.9702) were found. Conclusion: The results indicate that ACE genotypes interact differently with the same risk factors in each individual, influencing the development of CAD.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients.

AIMTo investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients.METHODSIn the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively.RESULTSForty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%).CONCLUSIONACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.

The relationship between angiotensin-converting enzyme (ACE) insertion (I) / deletion (D) polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.

Objective:In this study, we set out to investigate the relationship between angiotensin-converting enzyme (ACE) I/D polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.Methods:A standardized, structured, face-to-face interview was performed to collect demographic information. BMD was measured using dual-energy X-ray absorptiometry (DXA). I/D genotypes of ACE were determined by polymerase chain reaction (PCR) amplification. Serum ACE activity was determined photometrically by a commercially available kinetic kit. Multiple linear regression analysis was used to examine the relationship between ACE I/D polymorphism, serum ACE activity and BMD.Results:A total of 1567 males and 1760 females were selected for analyzing the relationship between ACE I/D polymorphism and BMD. There was no significant difference in spine BMD, total hip BMD and femur neck BMD among different ACE I/D genotypes both in males and females. A total of 1699 males and 1739 females were selected for analyzing the relationship between serum ACE activity and BMD. There was also no significant difference in spine BMD, total hip BMD and femur neck BMD among different serum ACE activity groups both in males and females.Conclusion:There was no relationship between ACE I/D polymorphism, serum ACE activity and BMD in older Chinese.

Association of I/D angiotensin-converting enzyme genotype with erythropoietin stimulation in kidney failure

Angiotensin-converting enzyme (ACE)-gene polymorphism is a possible predisposing factor of erythropoietin response under hypoxic conditions. However, it is not completely clear whether the ACE insertion/deletion (I/D) genotype has an impact on anemia in patients with permanent kidney failure. A 9-month prospective trial was conducted on 53 patients on hemodialysis aimed at determining the beneficial effect of oral vs intravenous iron in anemia management with recombinant human erythropoietin (rHuEpo), and identifying a possible association of the ACE gene I/D polymorphism with the response to rHuEpo. Patients were randomly allocated to receive 50-100 mg daily of ferrous gluconate orally (N=26) or intravenously every two weeks (N=27), together with rHuEpo-beta (200 IU/kg) subcutaneously, to achieve a hemoglobin increase to 105 g/L; subsequently the rHuEpo dose was adjusted at one or two week intervals. In 34 patients who regularly received ACE-inhibitor (ACEi) medication, genotyping for ACE-gene I/D polymorphism was performed using PCR, gel analysis and appropriate restriction digestion. After prolonged rHuEpo treatment, 24.5% of patients attained the targeted 9th-month hemoglobin concentration (105 g/L). Of these, 6/26 of patients received elemental iron orally and 7/27 received it intravenously. We observed an association between homozygous DD (deletion) of the ACE gene and a remarkable early increase in blood hemoglobin (p=0.028), erythrocyte count (p=0.020) and hematocrit (p=0.043) after reduction of the dose of rHuEpo (F=3.95; p=0.029), irrespective of the iron repletion mode (p=0.960). This is the first report on DD genotype as a linkage marker for the optimization of rHuEpo dose for anemia management in hemodialysis patients.

Association of Angiotensin-Converting Enzyme Gene Polymorphisms and Nephropathy in Diabetic Patients at a Tertiary Care Centre in South India.

Background:Genetic polymorphisms of the angiotensin-renin pathway have been thought to influence the development of diabetic nephropathy. However, there are conflicting results regarding this association in previous studies on populations with varying ethnicity.Aims:Primary aim was to compare the frequency of distribution of angiotensin-converting enzyme (ACE) gene (insertion/deletion [I/D]) polymorphism in Tamilian Indian type 2 diabetic individuals with and without microalbuminuria. Secondary objective was to compare the frequency of distribution of the 3 genotypes in diabetic patients with urinary albumin/creatinine ratio (ACR) < 30 mg/dL, urinary ACR = 30 to 300 mg/dL, and urinary ACR > 300 mg/dL.Methods:A total of 179 consecutive diabetic individuals between 40 and 70 years, from Puducherry and Tamilnadu of Dravidian descent participated in the study conducted from 2012 to 2014. Inclusion criteria were as follows: age ≥ 40 years and duration of type 2 diabetes mellitus for ≥5 years. Patients were divided into 2 groups based on ACR values. Group 1 consisted of 50 individuals with urinary ACR < 30 mg/g of creatinine, and group 2 consisted of 129 individuals with urinary ACR > 30 mg/g. Angiotensin I–converting enzyme (ACE) gene polymorphism was determined by allele-specific polymerase chain reaction method using a primer pair flanking the polymorphic region of its intron 16. Furthermore, group 2 patients were subdivided into those with urinary ACR = 30 to 300 mg/g of creatinine and those with urinary ACR > 300 mg/g of creatinine, and distribution of ACE gene polymorphism was compared in the three groups.Statistics:Statistical analysis was done using SPSS version 17.0. Independent Student t test was used to compare mean values between the 2 groups. Odds ratio was calculated for testing association between ACE gene (I/D) polymorphism and presence of microalbuminuria. P < .05 was considered significant. Comparison of ACE genotypes among 3 groups of patients (ACR < 30 mg/g, ACR = 30-300 mg/g, and ACR > 300 mg/g) was done using 1-way analysis of variance with Bonferroni multiple comparison test as post hoc analysis.Conclusions:Heterozygous I/D genotype was more frequent in the study population (45.8%) than the other genotypes. There was no difference in the genotype distribution in patients with varying levels of albuminuria.

Association between angiotensin-converting enzyme insertion/deletion gene polymorphism and end-stage renal disease in lebanese patients with diabetic nephropathy.

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD). The development and progression of nephropathy is strongly determined by genetic factors, and few genes have been shown to contribute to DN. An insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was reported as a candidate gene predisposing to DN and ESRD. Accordingly, we investigated the frequency of ACE I/D polymorphism in 50 patients with DN, of whom 33 had ESRD and compared them with 64 patients with type 2 diabetes mellitus (T2DM) but with normal renal function. Polymerase chain reaction amplification, using specific primers, was performed to genotype ACE I/D. Chi-square test was used to assess the differences between the groups. The frequencies of the ACE genotypes were as follows: 48% D/D, 40% I/D, and 12% I/I in patients with DN in contrast to 32.8% D/D, 45.3% I/D, and 21.9% I/I in T2DM. The distribution of the D/D, D/I, and I/I genotypes did not significantly differ between T2DM and DN. However, having the D allele carried a risk for the development of DN [odds ratio (OD), 1.71, P = 0.054]. On the other hand, the distribution of the D/D, D/I, and I/I genotypes was significantly different between T2DM and ESRD patients, χ2 = 7.23, P = 0.027. This was reflected by the D allele which carried a risk for the development of ESRD (OR, 2.51, P = 0.0057). These findings suggest that the D allele may be considered as a risk factor for both the development of DN and the progression of DN to ESRD in Lebanese population with T2DM.

The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and nicotine dependence in schizophrenia patients.

We investigated the relationship between the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk of nicotine dependence in Croatian schizophrenia patients. We also tested whether interactions between ACE-I/D polymorphism and smoking status affected the clinical psychopathology findings in patients as measured using Positive and Negative Symptom Scale (PANSS) scores. Polymerase chain reaction analysis was used to genotype 267 chronically ill schizophrenia patients (140 males/127 females). There were no significant differences in the distribution of ACE genotypes and alleles in male or female schizophrenia patients who were stratified based on their smoking status. However, there was a trend toward a difference in the ACE genotype distribution in female smokers vs. nonsmokers (χ 2=5.13, p=0.077) that was due mainly to the significant overrepresentation of ACE-ID heterozygous genotypes in female smokers compared to nonsmokers (62.3 vs. 42.0%, p=0.025). ACE-ID heterozygous females had about a twofold higher smoking risk than ACE-II and ACE-DD homozygous carriers (OR=2.29, 95% CI 1.1-4.7, p=0.026). We observed no contribution of the ACE genotype-smoking interaction to PANSS psychopathology. This is the first study to investigate the possible association between ACE-I/D polymorphism and nicotine dependence in schizophrenia. Our results suggest that the ACE-I/D polymorphism may be relevant in determining the risk of nicotine dependence in female patients with schizophrenia while the ACE genotype-smoking interaction does not contribute to the clinical expression of schizophrenia.

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients.Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed.Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05).Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

The Association of ACE Genotypes on Cardiorespiratory Variables Related to Physical Fitness in Healthy Men.

Aerobic power (VO2max), aerobic capacity (RCP), and running efficiency (RE) are important markers of aerobic fitness. However, the influence of the angiotensin converting enzyme (ACE) polymorphism on these markers has not been investigated in healthy individuals. One hundred and fifty physically active young men (age 25 ± 3 years; height 1.77 ± 0.06 m; body mass 76.6 ± 0.9 kg; VO2max 47.7 ± 5.5 ml·kg-1·min-1) visited the laboratory on two separate occasions, and performed the following tests: a) a maximal incremental treadmill test to determine VO2max and RCP, and b) two constant-speed running tests (10 km·h-1 and 12 km·h-1) to determine RE. The genotype frequency was II = 21%; ID = 52%; and DD = 27%. There was a tendency for higher VO2max with the ACE II genotype (p = 0.08) compared to DD and ID genotypes. Magnitude based inferences suggested a likely beneficial effect on VO2max with the ACE II genotype. There was no association between genotypes for other variable. These findings suggest that individuals with the ACE II genotype have a tendency towards better values in aerobic power, but not with aerobic capacity or running economy.

The lack of association between angiotensin-converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis.

ObjectiveBlood‐borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin‐converting enzyme (ACE), an enzymatic cascade known as the renin–angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE‐I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE‐I/D polymorphism might influence smoking behavior among patients with MS.Patients and MethodsGenotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.ResultsWe revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE‐I/D polymorphism and either pack‐year smoking history or number of cigarettes smoked daily (p > .05, respectively).ConclusionThe ACE‐I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE‐I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.

Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study.

BackgroundAccording to the WHO report in 2015, obesity is the fifth leading cause of death worldwide, and the prevalence of Egyptian female obesity is 37.5 %. Since obesity is highly influenced by genetics, and adipose tissue renin-angiotensin system is over-activated in obesity, the effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on obesity and related disorders was studied in several populations, because of its effect on ACE activity. Our objective was to study the association of ACE I/D polymorphism with obesity and certain related disorders, namely hypertension, insulin resistance and metabolic syndrome, in Egyptian females.MethodsEighty female volunteers were recruited, blood pressure and body measurements were recorded and a fasting blood sample was obtained for the quantitation of glucose, lipid profile, insulin, leptin and identification of ACE I/D polymorphs. Subjects were grouped based on hypertension and obesity states. Comparisons of continuous parameters were made with independent sample t-test between two groups. The frequencies of ACE genotypes and alleles, and the association between gene polymorphism and metabolic parameters were assessed using chi-square or Fisher's exact test.ResultsGenotype frequencies were in Hardy-Weinberg equilibrium for all groups. Genotype distribution did not differ significantly between controls and cases of all the studied disorders. Although DD carriers had apparently higher parameters of blood pressure, lipid profile and insulin resistance, only diastolic blood pressure was almost significant (p = 0.057). I-carriers were significantly less susceptible to hypertension than DD carriers having normal waist/hip ratio (p = 0.007, OR = 17.29, CI = 1.81–164.96) and normal conicity index (p = 0.024, OR = 7.00, CI = 1.36–35.93). In DD genotype carriers, a significant association was found between insulin resistance and high body mass index (p = 0.004, OR = 8.89, CI = 1.94–40.71), waist circumference (p = 0.003, OR = 9.63, CI = 2.14–43.36) and waist/height ratio (p = 0.034, OR = 6.86, CI = 1.25–37.61), although the variations in percentages between DD and I-carriers were not high enough to conclude an effect of ACE I/D on such an association.ConclusionsIn this sample of Egyptian females, ACE I/D polymorphism was not significantly associated with obesity nor with any of its related disorders studied. The I allele seemed protective against hypertension in subjects with normal, not high, waist/hip ratio and conicity index compared to DD genotype carriers.

INFLUENCE OF ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISM ON PREGNANCY OUTCOME IN WOMEN WITH HISTORY OF PRE-ECLAMPSIA

Background: Women who have had pre-eclampsia (PE) are more prone to recurrent negative pregnancy outcomes and altered utero-placental and umbilical flows in their future pregnancy. In addition, to an increased risk of later cardiovascular diseases, which clearly suggest a shared aetiology. Yet, the mechanisms involved have not been identified. Although, the causes of PE are not well understood, there is a possibility that PE has, at least in part, a genetic basis. The physiological remodelling of spiral arteries throughout pregnancy is mediated by the rennin-angiotensin system (RAS). The ACE I/D polymorphism of the ACE gene accounted for 47% of total phenotypic variance of the serum Angiotensin converting enzyme (ACE), contributing much to the variability of the ACE level. Previous studies failed to reproduce a persistent link of ACE I/D genotype and PE in nulliparous women. Objective: In this prospective study, we analysed the association of the ACE genotype and the recurrence of PE and/or fetal growth restriction (FGR) in subsequent pregnancy in women at high risk for a previous PE as primipara, without other known risk conditions. Patients and Methods: Sixty women with history of PE as primipara, with no known risk factors apart from nulliparity, were recruited in their second pregnancy. Their ACE genotyping were detected. Uterine arteries resistance indices (RI) and umbilical artery pulsatility index (PI), were recorded at 16th, 20th, 24th weeks of gestation and clinical pregnancy outcome was analyzed, as well. Results: ACE I/D genotype distribution among our cases of 90 Egyptian pregnant women were compatible to other races in literature. DD genotype was detected in 41.1% of our cases, 34.4% were ID genotype and 24.4% were II genotype. Significant difference in ACE I/D genotype and D-allele frequency were observed in cases with recurrent PE and/or FGR. Mid trimester uterine arteries resistance indices (RI) at 16th, 20th, 24th weeks of gestation, and umbilical artery pulsatility index (PI) at 20th, 24th weeks were significantly higher in DD genotype group compared to ID and II genotype respectively. In addition, DD genotype group had significantly lower gestational age at time of delivery, lower birth weight and placental weight. Conclusion: ACE DD genotype and D- allele frequency adversely affected pregnancy outcome and utero-placental and umbilical flow velocimetry in women with history of preeclampsia as nulliparous without known risk factors apart from nulliparity.

Impact of ACE I/D gene polymorphism on blood pressure, heart rate variability and nitric oxide responses to the aerobic exercise in hypertensive elderly

Abstract Objective To analyze the impact of I/D polymorphism of the angiotensin-converting enzyme gene on the responses of 24 h blood pressure, heart rate variability and nitric oxide after moderate aerobic exercise session. Method Twenty seven hypertensive elderly were genotyped for the I/D polymorphism of the angiotensin-converting enzyme gene (D/D: n = 9; I/D: n = 9; I/I: n = 9) and performed a bout of aerobic exercise at 90% of anaerobic threshold. Measurements of mean blood pressure, heart rate variability and nitric oxide were performed before and during 24 h post-aerobic exercise session. Results The D/D genotype showed impaired mean arterial pressure responses (elevation) in the nocturnal sleep (10:30 pm to 06:30 am) post-aerobic exercise when compared to rest (D/D= −4.2 ± 8.1 mmHg; p > 0.05, I/D = −9.2 ± 9.1 mmHg; p p p p > 0.05), showed reduced elevation of nitric oxide between genotypes immediately after aerobic exercise (D/D = 12.8 ± 135.3 μM and I/D = −8.7 ± 69.0 μM vs. I/I = 132.9 ± 188.7 μM; p p p Conclusion Elderly hypertensive individuals carrying the D/D genotype of the angiotensin converting enzyme gene showed impaired responses of blood pressure post-aerobic exercise, especially during sleep, and reduced heart rate variability during the 24 h post-aerobic exercise. Besides, to angiotensin converting enzyme genotypes with the presence of D allele (D/D and I/D) was impaired release of nitric oxide post-aerobic exercise session.

The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa

Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation.

Association between angiotensin-converting enzyme gene polymorphism and competitive anxiety in Tunisian athlete

The present study attempted to test whether the angiotensin-converting enzyme (ACE) genotypes can be associated with precompetitive anxiety that can be potentially used as predictors of athletic performance. Eighty-seven track and field athletes (47 males, 40 females; age 20.55 ± 2.22 years; body mass = 77.5 ± 7.1 kg, height = 170.7 ± 5.4 cm) competing at an international level voluntarily participated in this study. The athletes were prospectively classified into two groups according to their genetic polymorphism to physical efforts: endurance group (allele I, n = 48) and power group (allele D, n = 39). Suggested, this genetic predisposition was specifically associated with athlete’s success in sports. Precompetitive anxiety was assessed before competition, and the ACE gene polymorphism was examined by polymerase chain reaction. It was found that the score performances were associated with psychological factors. In carriers of allele I (related to the endurance), the self-confidence explained 18 % of the variance of score performance (R = 0.46, R 2 = 0.21, adjusted R 2 = 0.15; F = 3.83, p < 0.02). In carriers of allele D (related to the power) (R = 0.30, R 2 = 0.09, adjusted R 2 = 0.01; F = 1.19, p < 0.33), any factors of anxiety can explain the variance of performance. The current study is the first to interpret the relationship between the ACE gene and somatic anxiety, cognitive anxiety and self-confidence in sportsmen and has provided evidence of association between ACE I/D polymorphism predisposition and success in distance runners. Taking into account the effects of multiple comparisons, this result should be interpreted with caution and needs confirmation in a larger sample.

Influence of Angiotensin-converting Enzyme Genetic Polymorphism on Late Renal Dysfunction After Adult-to-adult Living-donor Liver Transplantation

BackgroundLate renal dysfunction (LRD) is known to be one of the most important complications to affect long-term outcome after living-donor liver transplantation (LDLT). The relationship between angiotensin-converting enzyme insertion (I)/deletion (D) gene polymorphism and renal function after LDLT are still unknown. The aim of this study was to elucidate the risk factors for LRD after LDLT, focusing on ACE gene polymorphism. Materials and MethodsAmong the 94 recipients who underwent adult-to-adult LDLT between March 2002 and September 2009, the total number of subjects who survived more than 1 year after LDLT and in whom angiotensin-converting enzyme genotype could be measured was 64. LRD was defined as estimated glomerular filtration rate level less than 60 mL/min/1.73 m2 at any point after 1 year from undergoing LDLT. ResultsLRD was found in 24 patients (37.5%). The incidence of LRD was significantly higher in D/D type than in I/I or I/D type: 85.7% (6/7) vs. 42.1% (8/19), 35.7% (10/38) (P = .010). Preoperative estimated glomerular filtration rate was significantly lower in D/D type than in I/I, I/D types, and postoperatively they were significantly lower in D/D type at 2, 3, and 4 years after LDLT. By multivariate analysis, age and hypertension were the independent risk factors for LRD. The 10-year survival rate was much lower in the recipients with LRD than in those without LRD at 66.7% versus 87.5%, respectively (P = .053). ConclusionIn conclusion, age and hypertension were determined as significant independent risk factors for LRD after adult-to-adult LDLT, and the recipients with D/D genotype should be strictly cared for the development of LRD.

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

Relationship of the rs1799752 polymorphism of the angiotensin-converting enzyme gene and the rs699 polymorphism of the angiotensinogen gene to the process of in-stent restenosis in a population of Polish patients with stable coronary artery disease

PurposeThe renin–angiotensin–aldosterone system may influence in-stent restenosis (ISR) via angiotensin II, which stimulates the production of growth factors for smooth muscle cells. The aim of this work is to assess the influence of the rs1799752 polymorphism of the angiotensin-converting enzyme (ACE) gene and the rs699 polymorphism of the angiotensinogen (AGT) gene on the ISR in Polish patients with stable coronary artery disease (SCAD) who underwent stent implantation. Material/methodsTwo hundred and sixty-five patients with SCAD were included in the study. All patients underwent stent implantation upon admission to the hospital and had subsequent coronary angiography performed. The patients were divided into two groups – those with significant ISR (n=53) and those without ISR (n=212). The ACE polymorphism was assessed using the classical PCR method and the AGT polymorphism was determined using the TaqMan method for SNP genotyping. ResultsNo difference in the frequency of angiographically significant ISR occurrence associated with the different ACE and AGT gene polymorphisms was observed. In a multivariable analysis, after correction for clinical variables, the relationship between the ACE and AGT genotypes within the scope of the analyzed polymorphisms and the process of restenosis was not found using a dominant, recessive and log-additive model. Late lumen loss was also independent of the genotypes of the polymorphisms before and after correction with angiographic variables. ConclusionsThe rs1799752 polymorphism and the rs699 polymorphism had no relationship with the occurrence of angiographically significant ISR and late lumen loss in a group of Polish patients who underwent metal stent implantation.