Mathematical modelling of the influence of ACE I/D polymorphism on blood pressure and antihypertensive therapy.

The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between ACE I/D and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between ACE I/D and the efficacy of inhibitors of the renin-angiotensin-aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different ACE I/D genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited.

POLYMORPHISM OF ACE AND AT2R1 GENES AS A GENETIC BACKGROUND FOR DIFFERENT TYPES OF ENCEPHALOPATHIES.

OBJECTIVE: The aim: To study the prevalence of ACE I/D and AT2R1 A1166C gene polymorphisms in patients with CTE, SVD, AIE, and PIE and to assess the influence of the presence of a particular genotype of the studied genes on the occurrence and/or progression of encephalopathies. PATIENTS AND METHODS: Materials and methods: A total of 96 patients with encephalopathies of various genesis (chronic traumatic encephalopathy (CTE) n=26; chronic alcohol-induced encephalopathy (AIE) n=26; microvascular ischemic disease of the brain (or cerebral small vessel disease, (SVD)) n=18; post-infectious encephalopathy (PIE) n=26) were involved in the study. The molecular genetic study was performed in the molecular genetics laboratory of the State Institution «Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine¼, Kyiv. Statistical processing of the results was performed using the STATISTICA 10.0 program. RESULTS: Results: In patients with various types of encephalopathies, probable changes in the frequency distribution of genotypes of polymorphic variants I/D of the ACE gene were established (11.11% vs. 33.33% - carriers of the I/I genotype, 27.78% vs. 50.00% - carriers of the I/D genotype and 61.11% vs. 16.67% - carriers of the D/D genotype) and A1166C of the AT2R1 gene (22.22% vs. 66.67% - carriers of the A/A genotype, 50.00% vs. 25.00% - carriers A/C genotype, 27.78% versus 8.33% - carriers of the C/C genotype) compared to individuals of the control group only in patients with SVD. The presence of the D allele and the D/D genotype of the ACE gene is associated with a statistically significant increase in the risk of SVD development and progression (respectively, 4.2 times (95% CI (1.39-12.72)) and 7.9 (95% CI ( 1.31-47.05)) times). A similar trend was established for the carrier of the C allele of the A1166C polymorphic variant of the AT2R1 gene in patients with SVD: a 4.3-fold increase in the risk of development and progression (95% CI (1.30-13.86). In addition, there is a probable dependence between carrier genotype A/C of the AT2R1 gene and increased risk of PIE and AIE by 4.8 and 5.7 times, respectively. CONCLUSION: Conclusions: Therefore, results suggest the reasonability to include the I/D of the ACE gene polymorphism investigation in the genetic panel of encephalopathies.

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases.

Background and Objectives: The COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. Patients and methods: This study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. Results: The frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p = 0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p < 0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p = 0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p = 0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants' genotypes (p = 0.016 and p = 0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. Conclusion: In conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.

Antecedentes y objetivos: La pandemia de COVID-19 surgió en China a fines de 2019 y se extendió rápidamente por todo el mundo. Existe evidencia de que la infección por COVID-19 puede verse influenciada por variaciones genéticas en el huésped. El objetivo de este estudio fue investigar la asociación entre el polimorfismo ACE InDel y COVID-19 en el norte de Chipre. Pacientes y métodos: Se incluyeron 250 pacientes diagnosticados de COVID-19 y 371 controles sanos. El genotipado del polimorfismo del gen ACE InDel se realizó mediante reacción en cadena de la polimerasa. Resultados: La frecuencia de homocigotos ACE DD aumentó significativamente en pacientes con COVID-19 en comparación con el grupo de control (p = 0,022). La diferencia en la presencia del alelo D entre los grupos de pacientes y control fue estadísticamente significativa (57,2% y 50,67%, respectivamente, p < 0,05). Las personas con el genotipo II tenían un mayor riesgo de COVID-19 sintomático (p = 0,011). Además, los hallazgos radiográficos de tórax se observaron con mayor frecuencia en individuos con el genotipo DD en comparación con los individuos con los genotipos ID y II (p = 0,005). Se encontró una diferencia estadísticamente significativa cuando se comparó el tiempo de aparición de los síntomas de COVID-19 y la duración del tratamiento con los genotipos de los participantes (p = 0,016 y p = 0,014, respectivamente). El tiempo de aparición de COVID-19 fue más corto en individuos con genotipo DD que en individuos con genotipo II, mientras que la duración del tratamiento fue más prolongada. Conclusiones: El polimorfismo ACE I/D podría predecir la gravedad de la COVID-19.

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases / Fuerte asociación entre el polimorfismo InDel del gen de la enzima convesiva de angiotensina y las enfermedades por COVID-19

Background and ObjectivesThe COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus.Patients and methodsThis study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction.ResultsThe frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants’ genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer.ConclusionIn conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19. (AU)

Antecedentes y objetivosLa pandemia de COVID-19 surgió en China a fines de 2019 y se extendió rápidamente por todo el mundo. Existe evidencia de que la infección por COVID-19 puede verse influenciada por variaciones genéticas en el huésped. El objetivo de este estudio fue investigar la asociación entre el polimorfismo ACE InDel y COVID-19 en el norte de Chipre.Pacientes y métodosSe incluyeron 250 pacientes diagnosticados de COVID-19 y 371 controles sanos. El genotipado del polimorfismo del gen ACE InDel se realizó mediante reacción en cadena de la polimerasa.ResultadosLa frecuencia de homocigotos ACE DD aumentó significativamente en pacientes con COVID-19 en comparación con el grupo de control (p=0,022). La diferencia en la presencia del alelo D entre los grupos de pacientes y control fue estadísticamente significativa (57,2% y 50,67%, respectivamente, p<0,05). Las personas con el genotipo II tenían un mayor riesgo de COVID-19 sintomático (p=0,011). Además, los hallazgos radiográficos de tórax se observaron con mayor frecuencia en individuos con el genotipo DD en comparación con los individuos con los genotipos ID y II (p=0,005). Se encontró una diferencia estadísticamente significativa cuando se comparó el tiempo de aparición de los síntomas de COVID-19 y la duración del tratamiento con los genotipos de los participantes (p=0,016 y p=0,014, respectivamente). El tiempo de aparición de COVID-19 fue más corto en individuos con genotipoDD que en individuos con genotipoII, mientras que la duración del tratamiento fue más prolongada.ConclusionesEl polimorfismo ACE I/D podría predecir la gravedad de la COVID-19. (AU)

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. PATIENTS AND METHODS: This study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. RESULTS: The frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants' genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. CONCLUSION: In conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.

The angiotensin-converting enzyme gene insertion/deletion polymorphism interacts with fear of falling in relation to stepping speed in community-dwelling older adults.

BACKGROUND: Despite the association of genetic factors with falls, balance, and lower extremity functioning, interaction of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with fear of falling (FOF) in relation to stepping performance has, to the best of our knowledge, not been investigated in older adults. OBJECTIVE: The purpose of this study was to examine the interaction effects of the ACE I/D polymorphism with FOF in relation to stepping performance in older adults. METHODS: Eighty-eight community-dwelling adults 60 years or older participated in a cross-sectional observational study. Participants completed tests of rapid and distance stepping, and self-reported FOF (yes/no). Participants provided saliva for ACE genotyping. General linear models evaluated ACE genotype × FOF interaction effects in relation to stepping performance. The α level was set at 0.05. RESULTS: The ACE I/D polymorphism exhibited significant interaction effects (p for interactions 0.002 ≤ p ≤ .04) with FOF in relation to stepping speed. Relationships between FOF and stepping speed varied among ACE genotypes. The insertion/insertion (II) genotype was significantly associated (p = .01) with slow stepping in individuals with, but not without FOF (p > .05). CONCLUSION: Variation in relationships between FOF and stepping speed among ACE genotypes suggests a role for the ACE I/D polymorphism in modifying relationships between FOF and stepping speed in older adults. The association of the ACE II genotype with slow stepping performance in individuals with, but not without FOF, suggests that older adults with the ACE II genotype and FOF may be at increased risk for poor stepping performance and associated functional declines.

Association of ACE I/D gene polymorphism and related risk factors in impaired fasting glucose and type 2 diabetes: a study among two tribal populations of North-East India.

BACKGROUND: Type 2 diabetes is a serious public health concern in India, even the indigenous tribal populations are not left unaffected. The present study aims to understand the association of major risk factors i.e. obesity, hypertension, dyslipidemia, ACE I/D polymorphism with impaired fasting glucose (IFG) and type 2 diabetes (T2D) among two different Mendelian populations of North East India. METHODS: Demographic, somatometric, physiological variables along with fasting blood samples were collected from 609 individuals. The participants were screened for ACE I/D polymorphism. RESULTS: ACE I/D polymorphism was found to follow HWE among Liangmai tribe but not among Mizo tribe. Distribution of DD genotype/D allele was found to be significantly higher for T2D among Mizo tribe. Significant association were observed between DD genotype/D allele of ACE I/D polymorphism and TC as well as LDL with both IFG and T2D only in Mizo tribe. CONCLUSIONS: The present study is an example of gene-environment interaction where DD genotype or D allele and dyslipidemia (high TC and high LDL) are posing risk for IFG and T2D both independently and in combination only among Mizo tribe with relatively less physical activity attributed to their residence in less hilly terrain however Liangmai tribe which resides in high hilly terrain shows no such association.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

INTRODUCTION: Diabetic nephropathy (DN) is the commonest single cause of end-stage renal failure, and dyslipidemia is a critical risk factor in the occurrence of DN. In the light of recent reports emphasizing the importance of angiotensin I-converting enzyme (ACE) in the modulation of plasma lipids, we sought to evaluate the influence of ACE I/D gene polymorphism with dyslipidemia status among type 2 diabetic (T2D) patients with and without nephropathy in the genetic predisposition and the progression to DN. METHOD: This study comprised of 600 subjects, which include patients with DN, T2D, and healthy controls (HC). Polymerase chain reaction based genotyping of ACE I/D polymorphism was performed and appropriate statistical analysis was done. RESULTS: Out of the 600 subjects, 20 (10%) of the HC, 73 (36.5%) of the T2D group, and 125 (62.5%) of the DN subjects had dyslipidemia. The D allele (0.62) and DD (42.5) genotype frequencies were higher in the DN group in comparison with T2D and HC (P < 0.05). The genotypes also varied among patients with dyslipidemia (χ2 5.04; P < 0.05) but not in the non-dyslipidemia group. Under the co-dominant model, DD genotype conferred a risk of 1.26 (P < 0.001) toward DN, whereas the ID genotype offered protection from DN among the dyslipidemic subjects (OR = 0.05; P < 0.01). In addition, genotype-dependent difference was seen in the plasma lipid levels among study groups. A multiple logistic regression analysis revealed male gender, BMI, HbA1c, TG, HDL, and ACE DD genotype as independent risk factors for the development of DN. CONCLUSION: The study showed a significant predisposing association of ACE DD genotype with DN and protective effect of ID genotype on DN in the dyslipidemia subgroup.

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

Abstract INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

Association of DD genotype of angiotensin-converting enzyme gene (I/D) polymorphism with hypertension among a North Indian population.

Hypertension, a major risk factor for cardiovascular diseases, is among the leading causes of morbidity and mortality worldwide. Genetic predisposition to the risk of developing hypertension due to angiotensin-converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism (through altered serum ACE activity) is well documented among various populations. The present study investigated the possible association between ACE (DD) genotype and hypertension using a nested case-control study design including 451 individuals (of either sex in the age group 30-65 years) from a rural North Indian population practicing agriculture and lacto-vegetarianism. Blood Pressure was classified using JNC-7 criterion. Age- and sex-matched individuals were selected from normotensive (N-122), pre-hypertensive (N-123), hypertensive not on medication (N-122), and hypertensive on medication (N-84) categories. Amplification of DNA and genotyping of PCR product was done using standard protocols. From the analysis, comparatively higher frequency of individuals with DD genotype in the hypertensive category was observed, indicating a possible relation between DD genotype and hypertension. The odds ratio analysis revealed 2.225 (1.13-4.37)-fold significant increased risk for hypertension among cases, validating the vulnerability of individuals with DD genotype towards hypertension. Thus, the present study highlights the increased risk for developing hypertension due to ACE DD genotype in the studied population.

Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

PURPOSE: To determine whether ACE2 I/D and BDKRB23 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R4+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-ß1 (TGF-ß1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. CONCLUSIONS: We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease.

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

BACKGROUND: According 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. METHODS: Eighty 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. RESULTS: Genotype 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. CONCLUSIONS: In 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.

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

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

Insertion/Insertion Genotype of Angiotensin I-Converting-Enzyme Gene Predicts Risk of Myocardial Infarction in North East India.

Myocardial infarction (MI) is common in India and the disease occurs at a relatively younger age. We wanted to look for association of Angiotensin I-converting enzyme (ACE) gene with MI in North East India. We also wanted to examine possible environmental interaction of ACE gene with established cardiovascular risk factors in causation of MI. In the study carried out in Assam Medical College, 200 consecutive confirmed cases of MI were recruited. Equal numbers of age- and sex-matched control subjects from hospital workers and patients attending the hospital for diseases unrelated to cardiovascular disease were enrolled. Structured questionnaires were used to note demographic and clinical factors. Cardiovascular risk factors were determined from history, physical examination and biochemical investigations. ACE insertion/deletion (I/D) polymorphism was determined by PCR method. Interaction of ACE gene with other risk factors was noted. The study identified ACE II genotype (odds ratio = 3.02; 95% CI 1.40-6.51), smoking, hypertension, diabetes and serum triglyceride > 150 mg/dl as independent risk factors for MI. ACE II genotype showed greater risk in non-smokers, non-hypertensives, non-diabetics and in subjects with LDL-C < 130 mg/dl. Low HDL cholesterol enhanced the genetic risk. Subjects with ACE II genotype have an independent risk of developing MI, specially in low cardiovascular risk subjects.

The ACE I/D polymorphism is associated with nitric oxide metabolite and blood pressure levels in healthy Mexican men / El polimorfismo I/D de la ECA se asocia con los niveles de metabolitos óxido nítrico y de presión arterial en hombres mexicanos sanos

The I/D insertion/deletion polymorphism of the angiotensin-converting enzyme has been related to hypertension. This polymorphism also seems to have gender related implications. Angiotensin II contributes to the production and release of oxygen reactive species that react with nitric oxide, inactivating its effects. Objective: To establish whether the ACE I/D polymorphism correlates with nitric oxide plasma metabolites in healthy men and women. Methods: Among 896 subjects between 18 and 30 years of age range, 138 fulfilled inclusion criteria. The polymorphism was identified by polymerase chain reaction, and blood nitric oxide metabolites were analyzed following the method described by Bryan. Results: Both systolic and diastolic arterial pressures were higher in men than in women (107/67 vs. 101/65 mmHg, p < 0.001). In terms of the ACE gene, there were differences in the concentration of nitric oxide metabolites in men with the I/D and D/D genotypes when compared to carriers of the I/I genotype (33.55 and 29.23 vs. 53.74 pmol/ml; p = <0.05), while there were no significant differences in women when compared by genotype. Men with the D/D genotype had higher systolic blood pressure than I/D carriers (111 vs. 104 mmHg, p < 0.05). We observed no arterial blood pressure differences in women when grouped by ACE genotype. Conclusions: The ACE D/D genotype was associated with nitric oxide metabolite levels and systolic blood pressure in clinically healthy men while it had no effect in women.

El polimorfismo inserción/deleción del gen de la enzima convertidora de la angiotensina (polimorfismo I/D de la ECA), se relaciona con hipertensión y sus efectos podrían estar asociados al género. La angiotensina II contribuye a la producción y liberación de especies reactivas de oxígeno, que reaccionan con el óxido nítrico (ON), inactivándolo. Objetivo: Conocer si existen diferencias en la concentración de metabolitos de ON en hombres y mujeres sanos que puedan estar influidas por el polimorfismo I/D de la ECA. Métodos: De 896 sujetos de entre 18 y 30 años, 138 cumplieron los criterios de inclusión. El polimorfismo fue identificado usando reacción en cadena de la polimerasa y los metabolitos de ON fueron analizados en sangre usando el método de Bryan. Resultados: Las presiones sistólica y diastólica fueron más elevadas en hombres que en mujeres (107/67 vs. 101/65 mmHg p < 0.001). En relación con el genotipo, existieron diferencias significativas en la concentración de metabolitos de ON en los hombres con genotipos I/D, D/D comparados con los portadores del genotipo I/I (33.55 y 29.23 vs. 53.74 pmol/ml, respectivamente; p = <0.05). No hubo diferencias significativas en las mujeres portadoras de los diferentes genotipos. Respecto a la presión arterial, los hombres con genotipo D/D presentaron mayor presión arterial sistólica que aquellos portadores de I/D (111 vs. 104 mmHg, p < 0.05). En las mujeres no se observaron diferencias significativas comparándolas por genotipo. Conclusiones: El genotipo D/D de la ECA está asociado con el nivel de metabolitos de ON en plasma y la presión arterial sistólica en hombres clínicamente sanos; esta asociación no se observa en las mujeres.

The ACE I/D polymorphism is associated with nitric oxide metabolite and blood pressure levels in healthy Mexican men.

UNLABELLED: The I/D insertion/deletion polymorphism of the angiotensin-converting enzyme has been related to hypertension. This polymorphism also seems to have gender related implications. Angiotensin II contributes to the production and release of oxygen reactive species that react with nitric oxide, inactivating its effects. OBJECTIVE: To establish whether the ACE I/D polymorphism correlates with nitric oxide plasma metabolites in healthy men and women. METHODS: Among 896 subjects between 18 and 30 years of age range, 138 fulfilled inclusion criteria. The polymorphism was identified by polymerase chain reaction, and blood nitric oxide metabolites were analyzed following the method described by Bryan. RESULTS: Both systolic and diastolic arterial pressures were higher in men than in women (107/67 vs. 101/65 mm Hg, p<0.001). In terms of the ACE gene, there were differences in the concentration of nitric oxide metabolites in men with the I/D and D/D genotypes when compared to carriers of the I/I genotype (33.55 and 29.23 vs. 53.74 pmol/ml; p=<0.05), while there were no significant differences in women when compared by genotype. Men with the D/D genotype had higher systolic blood pressure than I/D carriers (111 vs. 104 mm Hg, p<0.05). We observed no arterial blood pressure differences in women when grouped by ACE genotype. CONCLUSIONS: The ACE D/D genotype was associated with nitric oxide metabolite levels and systolic blood pressure in clinically healthy men while it had no effect in women.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in nutritional disorders in children.

PURPOSE: The aim of this study was to establish the role of angiotensin-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in determining obesity or undernutrition in a child population in Romania. METHODS: We assessed 293 consecutively hospitalized patients in a tertiary emergency pediatric hospital. The patients were divided, according to body mass index (BMI), into three groups: group I, the control group consisting of 126 children, group II patients with undernutrition (85 patients) and group III patients with obesity (82 patients). ACE I/D polymorphisms were performed in all three patient groups, as well as the measuring of anthropometric parameters [middle upper arm circumference (MUAC), tricipital skinfold thickness (TST)]. All patients also underwent paraclinical evaluations (protein and albumin). The cutoffs criteria for moderate undernutrition were: BMI between -2.0 SD and -3.0 SD, severe undernutrition: BMI <-3.0 SD, moderate obesity: BMI between +2.0 SD and +3.0 SD and severe obesity: BMI >+3.0 SD. RESULTS: We observed that DD genotype (64.7%) was prevalent in the moderate undernutrition group, while ID (35.3%) and II genotypes were higher in the subgroup of severe undernutrition, with significant correlations in DD and ID genotype groups between BMI and MUAC, protein and albumin (p < 0.0001). In the obese group, we observed significant correlations in DD genotype, between BMI and MUAC (p = 0.0014) and TST, and for II genotype, between BMI and TST (p = 0.0071). II genotype was associated with severe obesity, while D allele carriers were associated with moderate undernutrition and moderate obesity. CONCLUSION: BMI, MUAC, TST and serum protein levels are correlated with D allele carriers of ACE genes in children with moderate undernutrition and moderate obesity, whereas II genotype is an unfavorable prognostic factor corresponding to severe obesity and severe undernutrition.

The D allele of angiotensin-converting enzyme gene is associated with greater hemodynamic response to resistance exercises.

HYPOTHESIS/INTRODUCTION: The association of ACE I/D polymorphism and hemodynamic response to exercise have been limited to primarily aerobic exercises. We hypothesized that D allele carriers would show greater hemodynamic response to resistance exercise, as has been observed with aerobic. This study aimed to investigate the association of ACE I/D polymorphism and hemodynamic (blood pressure (BP), heart rate (HR) and rate-pressure product (RPP)) response to resistance exercise in young healthy subjects. MATERIALS AND METHODS: ACE I/D polymorphisms were studied by PCR analysis from 75 healthy men. Subjects completed a resistance exercise session of three sets of 10 knee extension repetitions with loads of 50, 75 and 100% of 10RM and two-minute rest intervals. Hemodynamic measures were recorded before and immediately after each set. Analysis of variance was used to identify significant differences among ACE genotypes. RESULTS: ACE I/D polymorphism is associated with hemodynamic response to resistance exercise, as healthy subjects with ACE D allele were prone to higher responses. In addition, this phenotypic difference seems to be a load-dependent trend. CONCLUSION: ACE DD carriers exhibit greater heart work during resistance exercise. Future studies should focus on the influence of resistance training period with different workloads on the hemodynamic response in healthy individuals with different ACE genotypes.

Angiotensin converting enzyme insertion/deletion polymorphism is associated with increased adiposity and blood pressure in obese children and adolescents.

BACKGROUND: The insertion/deletion polymorphism in the gene encoding the angiotensin-converting enzyme (ACE I/D) was associated with arterial hypertension and obesity in adults, but the data in children are scarce and yielded contrasting results. We assessed the impact of the ACE I/D on blood pressure and obesity related traits in a Brazilian cohort of obese children and adolescents. METHODS AND RESULTS: ACE I/D was genotyped in 320 obese children and adolescents (64% of girls) aged 7-16years, referred for a weight-loss program. We observed an association of the D-allele with blood pressure and with pre-hypertension/hypertension in boys (odds ratio 2.44, 95% C.I. 1.34-4.68, p=0.005 for a codominant model). The D-allele, insulin resistance and body fat mass had independent and additive effects and explained 14% of the variance of pre-hypertension/hypertension. The BMI, waist circumference, and body fat mass were significantly higher in DD/ID boys than in II boys (p<0.005). Allelic associations with obesity related traits were independent of the association with blood pressure. No genotype associations were observed in girls. CONCLUSIONS: The D-allele of the ACE I/D polymorphism was associated with arterial hypertension and with obesity related traits in boys, but not in girls, in a cohort of obese children and adolescents. These associations were independent of each other, as well as of the effects of other confounding traits such as insulin secretion, insulin sensitivity and glucose tolerance. Our results are in agreement with experimental evidences suggesting that the renin-angiotensin system plays a role in the regulation of visceral adipose tissue accumulation.