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Objective & Background: The exact cause of hypertension is unknown in about 90 to 95% patients, known as essential hypertension. Genes may play a crucial role in the pathology of essential hypertension. Gene for angiotensin converting enzyme (ACE) is found on long arm of chromosome 17q23, where 287 base pair insertion or deletion (I/D) polymorphism may occur. This study was aimed to assess the association of I/D polymorphism of ACE gene with blood pressure (BP) in Patients of Khyber Pakhtunkhwa (KPK). Methods: This Descriptive Cross-sectional study was conducted from 1st June 2021 to 30th September 2021 at Kuwait Teaching Hospital, Peshawar. The genomic DNA was extracted from lymphocytes and PCR was performed for identification of ACE I/D polymorphism. Results: Total 181 individuals (121 Hypertensive and 60 normal) were enrolled in the study. The measured systolic and diastolic BP in cases were 153.91mmHg±12.65 and 92.94mmHg±5.72, respectively while in control were 118.20±17.13 and 74.12mmHg±7.58, respectively. The Deletion Homozygous (DD), Insertion Homozygous (II) and Deletion and Insertion Heterozygous (DI) genotypes in hypertensive patients were 47 (38.84%), 17 (14.04%) and 57 (47.10%) respectively while in Control group the DD, II and DI were 4 (6.66%), 25 (41.66%) and 31 (51.66%) respectively. This study showed association of DD genotypes of the ACE gene with hypertension as compared to healthy individuals. Conclusion: Individuals with DD genotype may have association with hypertension. polymorphism of ACE gene was proved to be an important genetic marker for essential hypertension in Patients of KPK. [ABSTRACT FROM AUTHOR]

Objective: Genetic polymorphisms in ACE and ACE2 genes are involved in the RAS regulation of blood pressure and their activity may confer susceptibility to hypertension. In addition, they may play a role in SARS-CoV-2 pathogenesis and the severity of COVID-19. This study aims to determine the effect of genetic variations in the ACE (rs4331) and ACE2 (rs2074192) genes with hypertension comorbidity on the severity of COVID-19 in the Indonesian population. Result: 186 patients were enrolled and assigned into the COVID-19 group (n = 95) and non-COVID-19 group (n = 91) in this cross-sectional study. GG genotype frequency was dominant in ACE gene, but there were no significant differences between the groups (p = 0.163). The two groups had a significant difference (p = 0.000) for the CC genotype frequency (0,37 vs. 0.01) in the ACE2 gene. The proportion of women with COVID-19 is higher (51%), but men with hypertension had more severe symptoms (44%). Men with hypertension comorbidity, GG (ACE), and TT (ACE2) genotypes tended to have moderate-to-severe symptoms (25%). Similarly, women with hypertension as well as GG and CT genotypes tended to have moderate-to-severe symptoms (21%). We conclude that hypertension and mutations in the ACE (rs4331) and ACE2 (rs2074192) genes affect the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Genetic polymorphisms in ACE and ACE2 genes are involved in the RAS regulation of blood pressure and their activity may confer susceptibility to hypertension. In addition, they may play a role in SARS-CoV-2 pathogenesis and the severity of COVID-19. This study aims to determine the effect of genetic variations in the ACE (rs4331) and ACE2 (rs2074192) genes with hypertension comorbidity on the severity of COVID-19 in the Indonesian population. Result: 186 patients were enrolled and assigned into the COVID-19 group (n = 95) and non-COVID-19 group (n = 91) in this cross-sectional study. GG genotype frequency was dominant in ACE gene, but there were no significant differences between the groups (p = 0.163). The two groups had a significant difference (p = 0.000) for the CC genotype frequency (0,37 vs. 0.01) in the ACE2 gene. The proportion of women with COVID-19 is higher (51%), but men with hypertension had more severe symptoms (44%). Men with hypertension comorbidity, GG (ACE), and TT (ACE2) genotypes tended to have moderate-to-severe symptoms (25%). Similarly, women with hypertension as well as GG and CT genotypes tended to have moderate-to-severe symptoms (21%). We conclude that hypertension and mutations in the ACE (rs4331) and ACE2 (rs2074192) genes affect the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in the development and progression of DR, the Angiotensin I-converting enzyme (ACE) gene stands out, which presents an insertion (I) or deletion (D) polymorphism of a 287 bp Alu repetitive sequence in intron 16. Thus, this study aimed to perform a systematic review with meta-analysis to elucidate the relationship between the ACE gene (I/D) polymorphism (rs1799752) and the development and progression of DR in type 2 diabetic patients. PubMed/MEDLINE, Embase, Web of Science, and Scopus databases were systematically searched to retrieve articles that investigated the association between ACE gene (I/D) polymorphism in DR patients. Sixteen articles were included in the systematic review. The results describe no significant association between the polymorphism and DR risk (OR = 1.12; CI = 0.96–1.31; and p = 0.1359) for genotypic analysis by the dominant model (II vs. ID+DD). Moreover, we also observed no significant association between the D allele on the allele frequency analysis (I vs. D) and the DR risk (OR = 1.10; CI = 0.98–1.23; and p = 0.1182). Forest plot analysis revealed that the discrepancy between previous studies most likely arose from variations in their sample sizes. In conclusion, I/D polymorphism appears to be not involved in the susceptibility to and progression of the DR in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Ischemic stroke, a prevalent neurological disease, is the major reason of serious disability and death worldwide. Methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms increase homocysteine levels which also raise the risk of vascular diseases. Angiotensin-converting enzyme (ACE) gene polymorphisms can cause vascular reorganization and disrupt arterial wall stability. The aim of this study was to explore how the MTHFR and ACE gene polymorphisms are related to acute ischemic stroke. A total of 200 individuals (102 acute ischemic stroke patients and 98 healthy controls) were included in this case–control research. MTHFR gene C677T (rs1801133) and A1298C (rs1801131) polymorphisms were studied through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays, ACE gene I/D polymorphism (rs1799752) was studied by PCR. The MTHFR C667T and ACE I/D polymorphisms did not show any statistically meaningful differences between healthy controls and acute ischemic stroke patients (P > 0.05). However, compared to healthy controls, acute ischemic stroke patients had almost nine-fold higher prevalence of the CC genotype based on the MTHFR A1298C polymorphism (P=0.024, OR=8.8, 95%Cl=1.27–208.2). Additionally, individuals with acute ischemic stroke had greater frequencies of the combined genotypes of MTHFR and ACE gene polymorphisms in the forms of CC/CC (C667T/A1298C), CC/DD (A1298C/ACE I/D) and CC/CC/DD (C677T/A1298C/ACE I/D) (P = 0.027, P = 0.015 and P = 0.037, respectively). A statistically significant correlation was assessed between MTHFR gene A1298C polymorphism and acute ischemic stroke. Additionally, it was discovered that the genotype combinations of CC/CC (C667T/A1298C), CC/DD (A1298C/ACE I/D) and CC/CC/DD (C677T/A1298C/ACE I/D) have risk-increasing effects on acute ischemic stroke. To employ these genetic variations as alternative treatments for ischemic stroke, these findings should be validated by more research. [ABSTRACT FROM AUTHOR]

Background: This study investigated the association of angiotensin–converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin–angiotensin–aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. Materials and Methods: The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. Results: The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants (p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39–8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48–21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62–8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22–5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08–11.77]; p < 0.03). Furthermore, the haplotype–based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. Conclusion: Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population. [ABSTRACT FROM AUTHOR]

Introduction: The ACE gene, responsible for blood regulation, cell growth, and maintaining balance within the body, impacts an individual’s physical performance. Variations in this gene, such as allele I (insertions) and allele D (deletions), lead to differing effects. Allele I decrease ACE activity, prolonging bradykinin’s presence, boosting heart and skeletal muscle contraction, beneficial for endurance training. On the other hand, allele D heightens angiotensin II activity, promoting muscle growth and cell proliferation, advantageous for strength-focused training. This study compares six-week endurance training results in subjects with different ACE ID and ACE DD genotypes. Methods: 17 non-athletic students aged between 20 and 22 were the focus of this research, split into two groups: 10 individuals with the ACE ID genotype and 7 with the ACE DD genotype, identified through PCR analysis of buccal cell samples. Initial data collection involved recording the number of push-up and sit-up completed in 3 minutes and the duration of a plank exercise. After a six-week endurance training program, final data was collected, allowing observation of the changes in performance metrics. Results: All participants showed progress, with a collective of 4 individuals achieving notable improvements: 3 with the ACE ID gene surpassed 20 push-up repetitions, while 1 with the ACE DD gene achieved the same; 2 ACE ID gene carriers exceeded 35 sit-up repetitions; and another 2 ACE ID gene carriers surpassed 1 minute in plank duration. Conclusion: The ACE ID genotype has more significant potential to increase endurance than ACE DD. Genetic data can be used to determine training orientation preferences. [ABSTRACT FROM AUTHOR]

Aim: This research aimed to investigate whether endothelial nitric oxide synthase of eNOS intron 4 polymorphism and ACE gene I/D polymorphism have a role in the enhancement of the progressive of ADPKD with regards to hypertension. Materials and methods: The research was executed on 50 members with ADPKD presented in some dialysis centers in Baghdad city/Iraq and 50 similar age healthy controls individuals. The eNOS gene polymorphisms (intron 4 VNTR 4a/b) and ACE gene polymorphism were determined by the polymerase chain reaction method. Results: In the current research shows the ACE gene polymorphism is independent factors for hypertension in the ADPKD patients with high significant factors (DD p<0.001); also for eNOS intron 4 gene polymorphisms were expressively different between ADPKD patients whose with hypertensive and whose with normotensive (4a p<0.001). Conclusion: This research investigated that ACE and eNOS gene polymorphisms are associated with ADPKD patients concerning hypertension. For future studies, it must investigate other gene polymorphisms that responsible for hypertension to reveal the relation effect on the progressive of ADPKD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between common single nucleotide polymorphisms (SNPs) in angiotensin converting enzyme (ACE) gene and the risk of in-stent restenosis (ISR) and/or the response to angiotensin converting enzyme inhibitor ACEI in individuals with stable coronary artery disease (CAD) after stent implantation. Methods: The total population of this study consisted of 200 Egyptian individuals divided into 2 groups - in-stent restenosis (ISR) and non ISR group). Genomic DNA was withdrawn from EDTA whole blood applying a spin column approach and ACE gene insertion/deletion (I/D) polymorphisms were determined by polymerase chain reaction (PCR). Results: Carriers of allele D of ACE gene were significantly more liable to ISR occurrence. However, carriers of allele I were significantly more liable to ISR occurrence after administration of ACEI. There is a negative interaction between DD genotype of ACE gene and ACEI administration on ISR after percutaneous coronary intervention (PCI). However, there is a positive interaction between II and ID genotype of ACE gene and ACEI administration on ISR after PCI with bare metal stents (BMS). Conclusion: It is beneficial to implement ACEI in therapeutic regimen in individuals with ID or II genotypes of ACE gene, especially with BMS implementation. [ABSTRACT FROM AUTHOR]

Background: Some studies have suggested that the insertion(I)/deletion(D) polymorphism of the Angiotensin-Converting Enzyme (ACE) gene may be associated with human longevity, especially in centenarians. However, this association is still controversial. Besides, there have been no studies in Peruvians. Aim: To describe the age distribution of the ACE polymorphism in a convenience sample of Peruvian older people. Subjects and methods: This was a cross-sectional study in 104 Geriatric Day Hospital patients in Lima, Perú. The ACE polymorphism was determined in all patients. For the purpose of association with age, the sample was divided into four categories: young (< 65), youngest-old (65–74), middle-old (75–84) and oldest-old (85 or more). Results: The distribution of genotype frequencies was consistent with a population in Hardy-Weinberg equilibrium (p = 0.62). The number (%) of D/D, I/D and I/I genotypes in the young was 2 (14.3%), 3 (21.4%) and 9 (64.3%), respectively; in youngest-old: 4 (11.4%), 15 (42.9%) and 16 (45.7%); in middle-old: 6 (12.2%), 20 (40.8%) and 23 (46.9%); and in oldest-old: 0 (0.0%), 4 (66.7%) and 2 (33.3%). A chi-square analysis showed no significant differences in genotype distribution between age groups (p = 0.647). Conclusion: No significant age differences were found in the distribution of the ACE polymorphism in this sample. Further studies with greater statistical power are recommended. [ABSTRACT FROM AUTHOR]

Epithelial cells of the endothelial surfaces incorporate a gene for angiotensin-converting enzyme (ACE) that encodes metallopeptidase proteins. In this work, molecular characterization of the ACE gene by investigating the presence of two specific variants of 287 bp fragment (Alu element), have been studied. Therefore, the insertion (I allele) and the deletion (D allele) of this gene fragment were controlled. A group of Jordanian patients with Type-I and Type-II Diabetes Mellitus (DM) was selected for this study. The investigated sample contains 26 subjects with Type-I DM, 45 subjects with Type-II DM in addition to a control group of 44 healthy subjects. ACE genotypes of the patients and control groups were achieved using PCR of the DNA amplification. Results reveal no significant statistical differences in ACE genotype distribution among the focus group and the control one. Therefore, there is no significant association between DM and ACE genotype distribution variants of the proposed insertion. The ACE gene polymorphism is not directly correlated to diabetes. [ABSTRACT FROM AUTHOR]

Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil. • Hypertension and poor placental perfusion are important features in preeclampsia (PE). • Ins/del polymorphism in the angiotensin converting enzyme (ACE) gene is not associated with PE in Brazilian pregnant. • Frequency of Estrogen nuclear receptor1-ESR1 gene polymorphisms/rs2234693 and rs9340799 is not altered in Brazilian PE women. [ABSTRACT FROM AUTHOR]

We report a 32‐week fetus conceived of consanguineous parentage which presented with severe early onset oligohydramnios and history of a similarly affected sibling in previous pregnancy. Ultrasonography and autopsy were inconclusive, prompting exome sequencing on fetal DNA. This resulted in identification of a homozygous novel 3′ splice‐site variation in intron 17 of the ACE gene (NM_000789.3:c.2642‐1G>A), confirming diagnosis of autosomal recessive renal tubular dysgenesis, and facilitating prenatal diagnosis in subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the largest contributor to newborn mortality, morbidity, and hospitalization in the first year of life worldwide. Previous studies have suggested the importance of genetic variation in the angiotensin-converting enzyme gene, including the angiotensin-converting enzyme gene insertion/deletion polymorphism, in association with preterm birth. The angiotensin-converting enzyme is a key component of the renin-angiotensin system that is involved in blood pressure homeostasis during pregnancy and also affects risk factors of preterm birth, including the regulation of fibrinolytic system, uteroplacental circulation, vascularization of the placenta, and inflammation.Objective: The results of previous studies investigating the association between the insertion/deletion polymorphism and susceptibility to preterm birth have been inconsistent, therefore, we have performed a case-control study and conducted a meta-analysis of related studies to clarify this association.Study Design: In a case-control genetic association study, performed on 217 women with a history of preterm birth and 158 women who experienced full-term pregnancy, the significances of associations between allelic and genotype frequencies and preterm birth were determined using Chi-square tests. Following the case-control study, PubMed, Scopus, Google Scholar, and HugeNavigator databases were systematically searched to identify relevant studies. Altogether, four eligible studies involving 369 cases and 559 controls were included in the meta-analysis. The strength of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism for preterm birth was estimated by odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs), using a fixed-effects model (Mantel-Haenszel method).Results: In our case-control study we did not detect a significant association of angiotensin-converting enzyme insertion/deletion alleles and genotypes with preterm birth. The results of the meta-analysis showed a significant association between the angiotensin-converting enzyme gene insertion/deletion and the risk of preterm birth under allelic, dominant, and recessive comparison genetic models (D vs. I: OR = 1.35, 95% CI = 1.11-1.65, p = 0.0033; DD + ID vs. II: OR = 1.52, 95% CI = 1.08-2.15, p = 0.0161; DD vs. ID + II: OR = 1.48, 95% CI = 1.07-2.04, p = 0.0184).Conclusions: The present meta-analysis suggests that the insertion/deletion polymorphism of the angiotensin-converting enzyme gene in mothers might be associated with preterm birth, however, further well-designed large replication studies involving various ethnicities are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to investigate the angiotensin-converting enzyme (ACE) gene associations with the clinical picture of the most frequent complications of acute myocardial infarction (MI). The study included 190 patients who underwent one or more MI included in the WHO Register of Acute Myocardial Infarction. All the patients underwent genetic research for the identification of allelic variants of the ACE gene (polymorphism I/D). It was found that the DD genotype of the ACE gene is associated with a more frequent occurrence of acute left ventricular aneurysm (ALVA) (OR = 2.46, 95% CI 1.08-5.63, p = 0.037, χ2 = 4.73). In the group of patients with acute left ventricular failure (ALVF), the picture looked different: the genotype II of the ACE gene was more frequent (OR = 2.86, 95% CI 1.35-6.08, p = 0.007, χ2 = 7.81). Patients in the group without ALVF were carriers of the allele D more often (77.1%) (p = 0.007, χ2 = 7.81). Discovered genetic associations favor the consideration of the ACE gene as a genetic predictor of the development of ALVA in the acute period of MI. Further study of this gene in combination with other genetic markers of MI, as well as analysis of distribution of the genotypes of the ACE gene among deceased patients who underwent MI, will allow us to understand the genetic mechanisms of the development of other complications of MI, in particular, ALVF. All this will ensure the development of new highly effective personalized approaches to the prevention and treatment of complications of acute MI and the improvement of immediate and remote prognosis of patients. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) is a component of the circulating renin-angiotensin system, which influences circulatory homeostasis through the degradation of vasodilator kinins and the generation of vasopressor angiotensin II. Various phenotypic characteristics such as diseases and human performances could be associated with genetic polymorphisms within the ACE gene. To date, one of the most well-studied genetic polymorphisms that has been shown to be associated with athletic performance is that of the ACE gene. Previous studies investigating the influences of polymorphisms and various phenotypic characteristics have produced inconsistent findings due to inter-ethnic variations in the distribution of the different ACE alleles. For example, some studies showed that the I allele was associated with fatigue resistance in skeletal muscle and endurance performance while the D allele had been associated with power or sprint performance. Nevertheless, controversy still exists regarding the above conclusion as related studies reported that the I allele was associated with a better power or sprint performance rather than with athletic endurance abilities. This article discusses the inter-ethnic variations of the distribution of the different ACE alleles in several ethnic groups such as in European, African, American, and Asian populations. Additionally, the influences of the ACE ID polymorphism on human physical fitness performances in European and other populations are discussed. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that both systemic and white adipose tissue-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (V˙ O2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To assess whether this response involves increased angiotensin II type I receptor (AT1R) activation, AT1R blocker (losartan) was used in a separate group of 3ACE mice with body weight and adiposity comparable to that in the other 3ACE animals. We suggest that fasting-induced lower adiposity observed in animals with 3ACE gene copies might be associated with a higher expense of energy reserves; this response did not involve AT1R activation. [ABSTRACT FROM AUTHOR]

Strenuous exercise affects immune system and stimulates the synthesis of pro-inflammatory cytokines, including interleukin 6 ( IL- 6) and the anti-inflammatory cytokines, mainly interleukin 10 ( IL- 10). IL- 6 and IL- 10 fluctuations can influence sleep quality. Many genetic tracts influence the immune system response to exercise. The angiotensin-converting enzyme ( ACE) insertion/deletion ( I/D) polymorphism (rs1799752) is one of the most investigated genetic variants correlated to the physical performance and immune system. The aim of this study was to evaluate: (a) the response to an exhaustive strength exercise in terms of IL- 6 and IL- 10 expression in relation to ACE polymorphisms; and (b) the sleep behavior in response to an exhaustive strength exercise in relation to ACE polymorphisms. All participants were subjected to the following procedures: (a) genotyping of ACE polymorphism, (b) assay cytokine expression ( IL- 6 and IL- 10) pre- and post-exhaustive exercise, and (c) evaluation of sleep parameters pre- and post-exhaustive exercise by actigraphy. We showed that after the exhaustive exercise: (a) the ACE I/I, I/D, and D/D genotypes underwent an increase in IL- 6 expression ( p < 0.05); (b) only I/I and I/D genotypes increased significantly the IL- 10 expression ( p < 0.05); and (c) D/D genotypes showed a deterioration of sleep parameters: Sleep Efficiency and Immobile Time decreased ( p < 0.05) while Moving Time increased ( p < 0.01); the I/I and I/D genotypes showed no changes in sleep parameters. The increase of IL- 10 observed in I/I and I/D genotypes could play a protective role on sleep. The ACE D/D genotype seems to be more exposed to sleep disturbance after exercise. [ABSTRACT FROM AUTHOR]

Introduction: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings.Material and Methods: The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes.Results: Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis.Conclusions: Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution. [ABSTRACT FROM AUTHOR]

Objective To analyze the correlationship of ACE I/D gene polymerphisms with the anti-hypertensive efficacy of irbesartan among essential hypertension （EH） patients in Yunnan han people. Methods One hundred EH patients hypertension were treated with irbesartan 150mg once daily for 4 weeks， and anti-hypertensive efficacy were monitored during the treatment. Results There was a significant difference between anti-hypertensive efficacy of irbesartan among different genotype groups， DD group＞ID group＞II group （P ＜ 0.05） ．Conclusions There is different therapy responsiveness in diffenent genotypes. ACE I/D polymorphism may be an important hereditary factor that impacts the efficacy of irbesartan. [ABSTRACT FROM AUTHOR]

Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients. [ABSTRACT FROM AUTHOR]

The article presents a study of the role of angiotensin-converting enzyme (ACE) gene I/D polymorphism in a Tunisian population with cystic fibrosis (CF). The selection of patients was based on clinical manifestations of gastro-intestinal or/and lung disease, and sweat chloride concentration's high levels. Genomic DNA was extracted from peripheral blood having the classical salting-out protocol.

Abstract: We studied the influence of the ACEAluI/D and NOS3 4b/a polymorphisms on the heart rate variability (HRV) and cardiovascular hemodynamics (CVH, by cardiac rheography) in rowers, including Candidates for Master of Sports (CMS, n = 6) and athletes with no rank (AWR, n = 16). It has been found that the VO2max (р < 0.001) and HRV (all indexes, p < 0.05) in the supine and standing positions were higher in the CMS athletes than in AWR athletes. The frequency of the I allele of the ACE genein the CMS group (58%) did not differ from the mean population value (n = 855, 48.4%) but was higher than in the AWR group (13%, p = 0.035), which was associated with increased HF regardless of VO2max (p = 0.029). The frequencies of genotypes of NOS3 4b/a did not differ between groups, but the 4a allele was associated with an increased VLF%. Thus, elevated HRV in trained athletes may be caused by genetic factors, among which the I allele of the ACE gene may play an important role. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. Materials and Methods: The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Results: Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. Conclusion: We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine. [ABSTRACT FROM AUTHOR]

Many of the previous studies indicated that the I/D polymorphism of ACE gene is associated with diabetes type-2. To validate the association of I/D polymorphism in ACE gene, a study was designed in non-diabetic (normal) and diabetic type-2 patients of unrelated Gujarati population. The random blood samples from 36 normal and 36 diabetic type -2 patients of above 45 years were collected for the studies. DNA was extracted from blood samples for PCR by using ACE specific primers. The gene and genotype frequencies were estimated for different alleles observed in diabetic as well as in normal healthy persons. In present study, all three genotypes that is, I/I (477bp), I/D (477/190bp), D/D (190bp) were observed in samples from normal and diabetic patients. Among all genotypes ID (58.3%) has maximum genotypic frequency in diabetic than Non diabetic individuals (44.4%), frequency of II (27.7%) is more in Non diabetic individuals than Diabetic individuals (19.4%) and genotypic frequency of DD (27.7%) is more in Non diabetic than Diabetic individuals (22.22%). The results were not in agreement with so many previous studies. However, recent findings of other studies conducted in different ethnic groups are similar to our findings which do not support that I/D polymorphism are associated with type-2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. Methods: The study group ( n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril ( n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. Results: Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 ( p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant ( p < 0.05). However, differences between the groups were insignificant ( p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. Conclusion: Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigated the ACE and IL-4 genes in FMF. [•] ACE gene may be an important molecular marker to predict FMF risk. [•] IL-4 gene may be an important molecular marker to predict FMF risk. [ABSTRACT FROM AUTHOR]

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors. [ABSTRACT FROM AUTHOR]

Highlights: [•] The ACE I/D is a strong candidate to influence exceptional longevity worldwide. [•] ACE D-allele and DD genotype confer some selective advantage that contributes to reach exceptional longevity. [•] The ACE gene could have pleiotropic effects over the lifespan (see below). [•] The ‘cardiovascular-risk’ D allele could play a favorable role at the end of the human lifespan. [ABSTRACT FROM AUTHOR]

Aim: This study was designed to investigate the beneficial effects of green tea administration on angiotensin converting enzyme (ACE) gene expression in CCl4-induced liver cirrhosis in rats. Materials and methods: A total of 24 male Wistar rats were divided into 3 groups as: Group 1, normal untreated rats; Group 2, CCl4- induced cirrhotic rats; Group 3: CCl4-induced cirrhotic + green tea treated rats. The beneficial effects of green tea were measured by alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin level, tissue malondialdehyde (MDA), super oxide dismutase (SOD), and catalase (CAT). The genomic DNA was isolated from excised tissue to determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. Results: Liver cirrhosis was indicated by high plasma ALT, direct bilirubin level, tissue MDA, and low SOD. The antioxidant enzymes SOD and CAT were low (P < 0.01) in cirrhotic and green tea-treated rats. High activity (P < 0.01) of ALT was observed in green teatreated cirrhotic rats. The total and direct bilirubin levels were high (P < 0.01) in CCl4-treated cirrhotic rats while they were low (P < 0.05) in green tea-treated cirrhotic rats. The tissue MDA was high (P < 0.01) in CCl4- and green tea-treated cirrhotic rats. ACE gene expression after 8 weeks of CCl4 treatment in cirrhotic rats was significantly high (P < 0.05), and was reversed in green tea-treated cirrhotic rats in comparison to controls. Conclusion: The administration of green tea tries to correct the deteriorative biochemical and genetic changes during CCl4-induced liver cirrhosis in rats. The long-term consumption of green tea has beneficial effects on abnormally increased ACE gene activity during liver cirrhosis caused by CCl4 administration in rats. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between ACE gene I/D polymorphism and thyroid-associated ophthalmopathy (TO) in the Turkish population. Materials and methods: A total of 105 patients with TO and 102 healthy control subjects were enrolled in this case-control study. Genomic DNA was extracted from peripheral blood leukocytes, and I/D polymorphism of the ACE gene (ACE) was determined using a polymerase chain reaction. Results: There were no marked changes in allelic frequencies and genotype distribution of ACE I/D polymorphism between patients and control subjects. The distribution of I/D polymorphism and allele frequencies of TO patients were not significantly different from those of the controls: DD genotype 34.3% vs. 41.2%; ID genotype 46.7% vs. 43.1%; and II genotype 19.0% vs. 15.7%; D allele 57.6% vs. 62.7%; I allele 42.4% vs. 37.3% (P > 0.05). Genotype and allele frequencies for men and women were also similar between the groups. Conclusion: Our data suggest that ACE gene I/D polymorphism does not constitute a risk factor for TO in the Turkish population. Further studies using greater numbers of patients from different populations are required to clarify the role of the ACE gene in conferring susceptibility to TO. [ABSTRACT FROM AUTHOR]

The angiotensin (Ang)-converting enzyme ( ACE) insertion/deletion (I/D) polymorphism determines Ang II levels, but its relationship with lupus nephritis (LN) in different populations is controversial. Objective: To describe the allelic and genotypic distribution of the I/D polymorphism in Mexican mestizos with LN and assess an association with histological classes. Methods: We included 24 patients with systemic lupus erythematosus (SLE) without nephropathy, 41 with LN, 144 healthy subjects, and 36 with primary glomerulonephritis (GMN). Three ACE I/D polymorphism genotypes-ID, DD, and II-were detected by PCR using peripheral blood genomic DNA. Results: Frequencies for II, ID, and DD were 0.29, 0.46, and 0.25 in the SLE group; 0.17, 0.63, and 0.20 in the LN group; 0.14, 0.5, and 0.36 in the GMN group; and 0.26, 0.52, and 0.22 among healthy subjects. The I/D polymorphism distribution according to histological class was class II: 1 II, 3 ID, and 1 DD; class III: 2 II, 10 ID, and 1 DD; class IV: 2 II, 9 ID, and 2 DD; class V: 2 II, 3 ID, and 4 DD; and class VI, 1 II. The histological classes with at least three patients had ID genotype as the most frequent except for class V. Conclusion: No association was identified between I/D polymorphisms of ACE and SLE, LN, or GMN in a Mexican population. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for effective disorders. However, the results are conflicting, with no reported studies on Egyptian depressed patients. This study aimed to assess ACE insertion / deletion (I/D) gene polymorphism among Egyptian depressed patients in order to clarify HPA system dysregulation, and to determine its possible association with severity of depression. This case/control study was conducted on 42 adult depressed patients, and 37 healthy controls were screened to detect genetic associations with unipolar major depression. Determination of ACE genotypes was performed for all subjects by real time PCR. Total serum cortisol levels were measured by ELISA. The frequencies of the DD, ID and II genotypes were 26.2%, 45.2%, and 28.2%, respectively among the cases, and 17.49%, 25.2%, and 56.41%, respectively among the controls. Significant differences in ACE genotype distribution were observed between cases and controls (p = 0.0384). Serum cortisol in patients show the highest value in the ID polymorphism while II polymorphism shows the lowest value of a.m. cortisol. Data illustrated a significant association of ID polymorphism with the more severity of illness. Our findings support that ACE gene I/D polymorphism and high D allele frequency are associated with depression, also hypercortisolimia is significantly higher in individuals with major depression compared to control among Egyptian adults. ACE gene polymorphism might provide a common link between developing depressive episode and dysfunctional HPA-axis. [ABSTRACT FROM AUTHOR]

Abstract: Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated. The frequency distribution of the II, ID and DD genotypes was 82 (30.6%), 128 (47.8%) and 58 (21.6%) in the NS patients and 9 (4.0%), 171 (76.7%) and 43 (19.3%) in the control samples respectively. In the Pakistani pediatric NS population, the II genotypic and allelic frequencies were found to be significantly associated with the disease (OR=6.755; C.I=3–14.9). No significant association was found between this polymorphism and the response to standard steroid therapy. Thus, in contrast to reports from other parts of the world, the II genotype was found to be significantly associated with NS in the Indian and Malay populations and in the Pakistani population described here. To our knowledge, this is the first report from Pakistan describing the association of the ACE I/D polymorphism with pediatric NS. On the basis of these results, it is suggested that analysis of the ACE (I/D) polymorphism should be performed for the early diagnosis in the high risk NS patients in South Asia. [Copyright &y& Elsevier]

Angiotensin-converting enzyme (ACE) gene has been associated with the pathogenesis and progression of chronic kidney diseases. Diabetic nephropathy has become leading cause of renal end stage disease (ESRD). An I/D polymorphism of angiotensin-converting enzyme (ACE) gene has been suggested as one of the risk factors for the progression of diabetic nephropathy. We analyzed the genotype and allele frequency distribution of ACE gene in 166 Type 2 diabetic patients without any complication (T2DM), 61 with diabetic nephropathy (DN), 50 with non-diabetic nephropathy (NDN) and 50 healthy individuals from western Indian population. ACE genotype was analyzed by PCR method. The D allele distribution for the ACE I/D polymorphisms was not significantly different between control group and patients with T2DM without any complication (41.0% vs. 45.2%, P = 0.461) and between control subjects and patients with non-diabetic nephropathy (NDN) (41.0% vs. 44.0%, P = 0.668). Frequency of the D allele (63.9% vs. 45.2%, P < 0.001) and DD genotype (I allele noncarrier) (44.3% vs. 25.3%, P = 0.006) of ACE gene was significantly higher in patients with diabetic nephropathy (DN) than in patients with T2DM without any complication. Results of the present study indicate that ACE gene polymorphism does not have significant influence on development of diabetes mellitus and nondiabetic nephropathy, whereas, the DD polymorphism in ACE gene has been associated with the development of diabetic nephropathy in the Western Indian population. [ABSTRACT FROM AUTHOR]

Introduction: Arterial hypertension is defined as systolic or diastolic blood pressure measurements higher than 95 age-gender-height percentile of the adopted reference values. Angiotensin-converting enzyme (ACE) is a component of renin-angiotensin system. ACE insertion/deletion (I/D) gene polymorphisms have been associated with the risk of various cardiovascular anomalies. Aim: The purpose of our study was to assess the possible association of ACE I/D polymorphism gene and secondary hypertension in children. Material and method: We genotyped 40 healthy and 38 hypertensive children and adolescents. The ACE I//D gene polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism technique utilizing specific primers. We compared the distribution of ACE I/D genotypes in the two study groups. Results: The results of the study showed that the frequency of I/D ACE genotype distribution in patients with hypertension (DD = 18.42%, ID = 68.42%, II = 13.16%) did differ significantly from genotype distribution in controls (DD = 47.5%, ID = 42.5%, II = 10%), and the DD genotype was not associated with secondary hypertension. Conclusion: In conclusion we demonstrate that ACE gene polymorphisms are genetic markers for secondary arterial hypertension in children. [ABSTRACT FROM AUTHOR]

To evaluate the interaction between the angiotensin-converting enzyme ( ACE) gene insertion/deletion (I/D) polymorphism and gender with individual blood pressure response to hydrochlorothiazide (HCTZ) in hypertensives, we enrolled 829 mild-moderate hypertensive patients. All subjects were given HCTZ (12.5 mg) orally each day for 6 weeks. A total of 776 patients completed the study. There was statistically significant interaction between the effects of genotype and gender on systolic ( P = 0.002) and diastolic ( P = 0.048) response after adjusting for covariables. Moreover, in each gender, the genotype that was associated with the greatest blood pressure response to HCTZ (DD homozygotes in men and II homozygotes in women) was also associated with the greatest increase in serum ACE activity in response to HCTZ. The results suggest that the I/D polymorphism of the ACE gene is associated with interindividual differences in the blood pressure response to a low dose of a diuretic in a gender-specific manner in the Han Chinese population with hypertension. [ABSTRACT FROM AUTHOR]

To valuate whether angiotensin converting enzyme (ACE) gene insertion//deletion (I//D) polymorphism and aldosterone synthase (CYP11B2) gene −−344T//C polymorphism are associated with individual response to hydrochlorothiazide (HCTZ) in the Han Chinese population with essential hypertension. We enrolled 829 mild//moderate hypertensive patients and 12.5mg of HCTZ was given daily. After 6 weeks, the results showed that the ACE I//D polymorphism, not the CYP11B2 −− 344T//C polymorphism, was associated with systolic blood pressure (SBP) response to HCTZ ( P == 0.009) in the Han Chinese population with essential hypertension, with no interaction. [ABSTRACT FROM AUTHOR]

Aim: Fibrosis is a finding showing that the process can be progressive in the spectrum of non-alcoholic fatty liver disease. Activated hepatic stellate cells cause fibrosis induced by angiotensin II. In this study the relation between ACE gene (I/D) polymorphism and steatosis, necro­inflammation and fibrosis in liver were investigated. Method: 29 females and 30 males (mean age: 53±10) whose necroin­flammatorty activity and fibrosis scoring in liver biopsies were made according to Brunt classification were included in the study. According to the histopathological findings in liver biopsies patients with non-alcoholic fatty liver disease were determined and ACE gene (I/D) poly­morphism was studied by using genomic DNA isolated from peripheral blood samples. Result: In patient groups DD genotype frequency was 86.4%, ID geno­type frequency was 5.1% and genotype II frequency 8.5%. In patient there was no significant relation between ACE gene (I/D) polymor­phism, and necroinflammatory activity and fibrosis. Conclusion: In patients the high frequency of D/D genotype but no association between necroinflammatory activity and fibrosis suggest that ACE gene had no role in the development of fibrosis in non-alco­holic fatty liver disease, however it is a component of general meta­bolic disorder. [ABSTRACT FROM AUTHOR]

Abstract: The coronary artery disease (CAD) is of the main causes of heart failure and there is evidence supporting the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and the susceptibility to CAD. Therefore, the relevance of ACE polymorphism for CAD was determined in the Iranian population. 487 age-matched individuals including 224 patients with >50% angiographically established coronary stenosis and 263 healthy subjects genotyped for ACE gene I/D polymorphism by a standard method. Paraclinical characteristics including lipid profile were also determined for both groups. While the systolic (p <0.0001) and diastolic (p <0.0001) blood pressure, serum cholesterol (p <0.005) and LDL-C (p <0.05) were significantly increased in CAD patients, our results show that there was no increased risk of CAD in association with DD genotype in Iranian population. Allele frequencies were also similar in both groups. Although, we found a significant difference in ID (p <0.005) and II (p <0.05) genotype between patients and healthy subjects. The present study showed that DD genotype does not increase the CAD susceptibility in the studied Iranian population and may not be as a risk factor. Therefore, further studies together with the other polymorphisms of ACE gene may be required to determine the relation between cardiovascular disease susceptibility and ACE genetic variations in Iranian population. [Copyright &y& Elsevier]

Abstract: The psocid, Liposcelis paeta Pearman, is an increasingly important polyphagous pest of stored products worldwide. Intensive use of organophosphorous insecticides for pest control has facilitated resistance development in psocids in China. Three insecticide-resistant field populations of L. paeta were collected from Nanyang city of Henan Province (NY), and Wuzhou (WZ) and Hezhou (HZ) cities of Guangxi Province, China. Previous studies have shown that psocids have different susceptibilities to insecticides. In addition, their AChE susceptibilities to paraoxon-ethyl and demeton-S-methyl also differed from each other. Acetylcholinesterase 1, which is one of the major targets for organophosphate insecticides, has been fully cloned and sequenced from these populations of L. paeta. Comparison of both nucleotide and deduced amino acid sequences revealed nucleotide polymorphisms among L. paeta ace 1 genes from different populations, but none of these polymorphisms correspond to the active sites in AChE 1 from other insects. The results of comparative quantitative real-time PCR indicated that the relative expression level of HZ ace 1 gene was the highest among three populations, which was 1.20 and 1.02-fold higher than those of NY and WZ populations, respectively. This may due to an epigenetic inheritance phenomenon, which allows organisms to respond to a particular environment through changes in gene expression. [Copyright &y& Elsevier]

1. Clinical and experimental evidence highlights the importance of the renin–angiotensin system in renovascular hypertension. Furthermore, genetic factors affecting angiotensin-converting enzyme (ACE) could influence the development of renovascular hypertension. 2. To test the effect of small gene perturbations on the development of renovascular hypertension, mice harbouring two or three copies of the Ace gene were submitted to 4 weeks of two-kidney, one-clip (2K1C) hypertension. Blood pressure (BP), cardiac hypertrophy, baroreflex sensitivity and blood pressure and heart rate variability were assessed and compared between the different groups. 3. The increase in BP induced by 2K1C was higher in mice with three copies of the Ace gene compared with mice with only two copies (46 vs 23 mmHg, respectively). Moreover, there was a 3.8-fold increase in the slope of the left ventricle mass/BP relationship in mice with three copies of the Ace gene. Micewith three copies of the Ace gene exhibited greater increases in cardiac and serum ACE activity than mice with only two copies of the gene. Both baroreflex bradycardia and tachycardia were significantly depressed in mice with three copies of the Ace gene after induction of 2K1C hypertension. The variance in basal systolic BP was greater in mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two copies of the gene (106 vs 54%, respectively). In addition, the low-frequency component of the pulse interval was higher mice with three copies of the Ace gene after 2K1C hypertension compared with those with only two (168 vs 86%, respectively). Finally, in mice with three copies of the Ace gene, renovascular hypertension induced a 6.1-fold increase in the sympathovagal balance compared with a 3.2-fold increase in mice with only two copies of the gene. 4. Collectively, these data provide direct evidence that small genetic disturbances in ACE levels per se have an influence on haemodynamic, cardiac mass and autonomic nervous system responses in mice under pathological perturbation. [ABSTRACT FROM AUTHOR]

Abstract: Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI]>5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age=48±13y, body mass index=29±5kg/m2, AHI=34±25events/h). HTN was present in 114 patients (43%) who were older (p <0.01), heavier (p <0.05) and had more severe OSA (p <0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p <0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR=1.12) and II genotype (OR=0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. [Copyright &y& Elsevier]

Background & Objective: Angiotensin converting enzyme (ACE) inhibitors are used widely in therapy for hypertension, congestive heart failure and myocardial infarction. However, coughing, one of their major adverse effects limits their use. It is documented that Asians are more liable to coughing than Europeans. The aim of this study was to investigate genetic polymorphism involved in ACE inhibitor-induced coughing. Methods: We monitored hypertensive subjects ( n = 110) treated with ACE inhibitors, and tested for any associations between ACE inhibitor-induced coughing and polymorphisms in the genes for ACE and the bradykinin B2 receptor, which are suspected to be related to coughing. Results & Discussion: We found no significant differences between the groups with coughing and without coughing in the frequency of ACE I/D (Insertion/Deletion) polymorphisms. One single nucleotide polymorphism was discovered in the promoter (−58T/C) and, one in intron-exon junction upsteam of exon 2 (−59C/A), of the bradykinin B2 receptor gene. However, no significant correlation was found between those genotypes or allele distributions and ACE inhibitor-induced coughing. Conclusion: We found no significant links between polymorphisms of the ACE gene or bradykinin B2 receptor gene with ACE inhibitor-induced coughing in hypertensive Koreans. But, the topic remains controversial and requires more study. [ABSTRACT FROM AUTHOR]

Aim: Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of glomerulonephritis leading to end-stage renal disease (ESRD). A few clinical and paraclinical factors are considered as contributing factors in progression rate. However, there are controversial reports on the relationship between ACE gene polymorphism and rapidity of progression of FSGS to ESRD in different populations. To elucidate this issue, we investigated the relationship between the insertion (I) and deletion (D) ACE gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children. Methods: Forty-one children aged 1–18 years admitted to St AlZahra Hospital, Isfahan, and St Ali Asghar Hospital, Tehran, Iran, with idiopathic FSGS were enrolled. Renal death was defined as a glomerular filtration rate (GFR) of less than 50 mL/min per 1.73 m2 or a decreased GFR to less than 50% compare to baseline. Reaching renal death in less or more than 2 years were labelled as rapid progressors (RP) or slow progressors (SP), respectively. Intron 16 of the ACE gene was amplified by the polymerase chain reaction technique. Results: Twenty-eight patients were male and 13 were female. In 15 RP patients, the genotype distribution was 26.6% DD, 6.7% II and 66.7% ID. In 26 SP patients, the genotype was similar (38.6% DD, 7.6% II and 53.8% ID, P > 0.05). There were no statistically significant differences for ACE I/D gene polymorphism between the two groups of patients ( P > 0.05). Conclusion: Our study revealed no correlation between ACE I/D gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children. [ABSTRACT FROM AUTHOR]

Abstract: Alterations of the structure and activity of the enzyme acetylcholinesterase (AChE) leading to resistance to organophosphate insecticides have been examined in the oriental fruit fly, Bactrocera dorsalis (Hendel), an economic pest of great economic importance in the Asia-Pacific region. We used affinity chromatography to purify AChE isoenzymes from heads of insects from lines showing the phenotypes of resistance and sensitivity to insecticide treatments. The AChE enzyme from a strain selected for resistance to the insecticide fenitrothion shows substantially lower catalytic efficiency for various substrates and 124-, 373- and 5810-fold less sensitivity to inhibition by paraoxon, eserine and fenitroxon, respectively, compared to that of the fenitrothion susceptible line. Using peptide mass fingerprinting, we also show how specific changes in the structure of the AChE enzymes in these lines relate to the resistant and sensitive alleles of the AChE (ace) gene characterized previously in this species (described in Hsu, J.-C., Haymer, D.S., Wu, W.-J., Feng, H.-T., 2006. Mutations in the acetylcholinesterase gene of Bactrocera dorsalis associated with resistance to organophosphorus insecticides. Insect Biochem. Mol. Biol. 36, 396–402). Polyclonal antibodies specific to the purified isoenzymes and real-time PCR were also used to show that both the amount of the isoenzyme present and the expression levels of the ace genes were not significantly different between the R and S lines, indicating that quantitative changes in gene expression were not significantly contributing to the resistance phenotype. Overall, our results support a direct causal relationship between the mutations previously identified in the ace gene of this species and qualitative alterations of the structure and function of the AChE enzyme as the basis for the resistance phenotype. Our results also provide a basis for further comparisons of insecticide resistance phenomena seen in closely related species, such as Bactrocera oleae, as well as in a wide range of more distantly related insect species. [Copyright &y& Elsevier]

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion–deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0 ± 11.36 years, age at onset of spondylarthropathy was 27.7 ± 7.49 years and disease duration was 10.3 ± 7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls ( p = 0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls ( p = 0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs. [ABSTRACT FROM AUTHOR]

The ACE and the LRPAP1 gene insertion-deletion polymorphisms were determined in 133 healthy individuals sampled from Ouangolodougou, a village located in northern Ivory Coast. No sex differences were found in ACE and LRPAP1 gene frequencies. The ACE insertion and deletion alleles had frequencies of 0.346 and 0.654, respectively. The ACE gene was not in Hardy-Weinberg equilibrium because of an excess of heterozygote genotypes and a deficiency of I/I genotypes compared to the expected values. Statistical analysis showed a significantly lower frequency of I/I genotypes in the Ivory Coast population compared to Sudan, Kenya, African Americans, and African Brazilians (p < 0.05), whereas no differences were found with respect to Somalia. Conversely, the frequencies of the insertion and deletion alleles in the Ivorian population did not differ from those of other African populations. The LRPAP1 insertion and deletion allele frequencies found in our study (0.192 and 0.808, respectively) did not differ significantly from the Czech and Spanish populations, the only two populations previously characterized for this polymorphism. However, the frequency of the I/I genotype was significantly lower than the frequencies observed in the European samples. Because of the limited information on the LRPAP1 gene polymorphism distribution in worldwide populations, it was not possible to draw any conclusion. [ABSTRACT FROM AUTHOR]

A great number of association studies have been performed to identify the genes involved in the etiology and prognosis of sarcoidosis. We performed a systematic review of case-control studies through the PubMed database and evaluated them for a possible inclusion into a meta-analysis in order to assess whether the reported genetic polymorphisms are the risk factors of sarcoidosis. Case-control studies with clear diagnostic criteria and interventions were included. Only investigations of a single polymorphism/gene involvement in sarcoidosis reported more than five times were selected. Aggregating data from 12 studies on ID/ACE polymorphisms, the odds ratio (OR) for sarcoidosis, if the polymorphism was considered under the dominant genetic model, was not significantly increased: 1.19 (95% CI 0.98–1.43); OR under the recessive model was 1.20 (95% CI 0.98–1.46). In seven case-control studies on −308/TNF-α polymorphism, the OR for sarcoidosis if the polymorphism considered under the dominant genetic model was significantly increased at 1.47 (95% CI 1.03–2.08); the OR under the recessive model was 1.39 (95% CI 0.67–2.90). In conclusion, the results showed that the TNF-α genotype could be a significant risk factor for sarcoidosis, whereas the risk of sarcoidosis due to the ACE genotype was not substantially elevated. [ABSTRACT FROM AUTHOR]

Abstract: Mutations in the gene encoding the enzyme acetylcholinesterase (AChE) of the oriental fruit fly, Bactrocera dorsalis, associated with resistance to an organophosphorus insecticide have been characterized. Three point mutations producing nonsynonymous changes in the predicted amino acid sequence of the product of the B. dorsalis ace gene in resistant vs. susceptible flies have been identified. One of these changes is unique to B. dorsalis while the other two occur at sites that are identical to mutations previously described for another Bactrocera species. Although the precise role of the third mutation is not clearly established, the independent origin of two identical alterations in these two species strongly supports the idea proposed previously that molecular changes associated with insecticide resistance in key genes and enzymes such as AChE are largely constrained to a limited number of sites. The results obtained here also suggest that the widespread use of organophosphorus insecticides will likely lead to a predictable acquisition of resistance in wild populations of B. dorsalis as well as other pest species. For surveys of B. dorsalis populations that may develop resistance, diagnostic tests using PCR-RFLP based methods for detecting the presence of all three mutations in individual flies are described. [Copyright &y& Elsevier]