Angiotensin-converting Enzyme Genotype Research Articles

Association between Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the susceptibility to psoriasis and oxidative stress (OS) in a cohort of pediatric psoriatic patients in Sri Lanka: A cross sectional study.

Pediatric psoriasis accounts for nearly one-third of the global psoriasis burden. Multiple lines of evidence have shown the relationship between Angiotensin-converting enzyme (ACE) Insertion (I)/deletion(D) polymorphism with psoriasis susceptibility, and oxidative stress (OS) in psoriatic patients. However, such studies, particularly on pediatric psoriasis, are scarce in the local setting. Our study investigated the prevalence of ACE I/D polymorphism and its associations with oxidative stress in pediatric psoriasis patients in Sri Lanka. Thirty patients were recruited for this study after obtaining ethical clearance. The polymerase chain reaction was used to explore the ACE I/D polymorphism. Serum Nitric Oxide (NO) levels and the Total Antioxidant Capacity (TAC) were measured using the Griess assay and the FRAP assay. Clinical details were obtained from the clinic reports. Female predominance (76.67%) in pediatric psoriasis was reported, while Plaque psoriasis (66.67%) was found to be the most prevalent form. I/D was reported as the predominant genotype (66.67%) while I/I and D/D genotypes were recorded in 23.33% and 10% of patients, respectively. Significantly higher NO levels were observed in I/D patients than in I/I patients but not among other groups. No differences in TAC among ACE genotypes were reported. This pilot study revealed female gender and I/D genotype with increased NO levels as risk factors for pediatric psoriasis in Sri Lanka. However, it is prudent to increase the sample size to further validate the results.

Cardiac biomarker responses following high-intensity interval and continuous exercise: the influence of ACE-I/D gene polymorphism and training status in men.

This study aimed to investigate the relationship between pre- and postexercise cardiac biomarker release according to athletic status (trained vs. untrained) and to establish whether the I/D polymorphism in the angiotensin-converting enzyme (ACE) gene had an influence on cardiac biomarkers release with specific regard on the influence of the training state. We determined cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in 29 trained and 27 untrained male soccer players before and after moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) running tests. Trained soccer players had higher pre (trained: 0.014 ± 0.007 ng/mL; untrained: 0.010 ± 0.005 ng/mL) and post HIIE (trained: 0.031 ± 0.008 ng/mL; untrained: 0.0179 ± 0.007) and MICE (trained: 0.030 ± 0.007 ng/mL; untrained: 0.018 ± 0.007) cTnI values than untrained subjects, but the change with exercise (ΔcTnI) was similar between groups. There was no significant difference in baseline and postexercise NT-proBNP between groups. NT-proBNP levels were elevated after both HIIE and MICE. Considering three ACE genotypes, the mean pre exercise cTnI values of the trained group (DD: 0.015 ± 0.008 ng/mL, ID: 0.015 ± 0.007 ng/mL, and II: 0.014 ± 0.008 ng/mL) and their untrained counterparts (DD: 0.010 ± 0.004 ng/mL, ID: 0.011 ± 0.004 ng/mL, and II: 0.010 ± 0.006 ng/mL) did not show any significant difference. To sum up, noticeable difference in baseline cTnI was observed, which was related to athletic status but not ACE genotypes. Neither athletic status nor ACE genotypes seemed to affect the changes in cardiac biomarkers in response to HIIE and MICE, indicating that the ACE gene does not play a significant role in the release of exercise-induced cardiac biomarkers indicative of cardiac damage in Iranian soccer players.NEW & NOTEWORTHY Our study investigated the impact of athletic status and angiotensin-converting enzyme (ACE) gene I/D polymorphism on cardiac biomarkers in soccer players. Trained players showed higher baseline cardiac troponin I (cTnI) levels, whereas postexercise ΔcTnI remained consistent across groups. N-terminal pro-brain natriuretic peptide increased after exercise in both groups, staying within normal limits. ACE genotypes did not significantly affect pre-exercise cTnI. Overall, athletic status influences baseline cTnI, but neither it nor ACE genotypes significantly impact exercise-induced cardiac biomarker responses in this population.

ACE I/D polymorphism is a risk factor for the clinical severity of COVID-19 in Brazilian male patients.

The renin-angiotensin system is potentially involved in the pathogen-host interaction in the disease caused by SARS-CoV-2, since the angiotensin-converting enzyme (ACE) 2 serves as a receptor for the virus. The impact of the pandemic in specific regions and ethnic groups highlights the importance of investigating genetic factors that disrupt the balance of the system in response to SARS-CoV-2 infection, especially in genes with ethnic frequency variations. Therefore, this study aimed to evaluate the influence of the ACE I/D polymorphism on the incidence and severity of COVID-19 in a sample of the Brazilian population. 70 severe cases and 355 mild cases patients were evaluated. DNA extraction was performed using a QIAamp DNA Blood Mini kit. Genotyping of ACE I/D polymorphism was performed. Clinical outcomes were obtained from the patients' records. We found an association between the ACE I/D polymorphism and the incidence or severity of COVID-19 in male participants. Moreover, we observed a relationship between severity and increasing age and body weight and a higher frequency of II genotype individuals among those who had a cough as their symptoms in mild patients. No differences were observed in leukocyte count or other parameters related to the inflammatory response in severe patients. Our data showed the influence of the ACE I/D polymorphism on severity of COVID-19 in males, as well as on the occurrence of cough in patients with mild symptoms, with a higher incidence in those carrying the I allele.

ACE gene polymorphisms (rs4340) II and DI are more responsive to the ergogenic effect of caffeine than DD on aerobic power, heart rate, and perceived exertion in a homogeneous Brazilian group of adolescent athletes.

The purpose of this study was to verify the association between angiotensin-converting enzyme (ACE) genotypes DD, DI, and II and caffeine (CAF) ingestion on endurance performance, heart rate, ratio of perceived exertion (RPE), and habitual caffeine intake (HCI) of adolescent athletes. Seventy-four male adolescent athletes (age: DD=16±1.7; DI=16±2.0; II=15±1.7 years) ingested CAF (6 mg/kg) or placebo (PLA) one hour before performing the Yo-Yo Intermittent Recovery level 1 (Yo-Yo IR1) test. No difference was found among groups for HCI. However, CAF increased the maximal distance covered and VO2max in DI and II genotype carriers compared to PLA (DD: Δ=31 m and 0.3 mL·kg-1·min-1; DI: Δ=286 m and 1.1 mL·kg-1·min-1; II: Δ=160 m and 1.4 mL·kg-1·min-1). Heart rate of DI and II genotype carriers increased with CAF compared to PLA, while RPE was higher in the II and lower in the DD genotypes. The correlations between HCI and maximal distance covered or VO2max were significant in the II genotype carriers with CAF. CAF increased endurance capacity, heart rate, and RPE in adolescent athletes with allele I, while endurance performance and aerobic power had a positive correlation to HCI in the II genotype group. These findings suggested that DD genotype were less responsive to CAF and that genetic variations should be taken into account when using CAF supplementation to enhance exercise performance.

Association between Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism with Diabetic Peripheral Neuropathy and Its Importance as a Genetic Biomarker

Background: Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of type 2 diabetes mellitus (T2DM) with a prevalence ranging from 18.8% to 61.9% in India. For patients with T2DM, identifying those who are at risk of developing DPN is crucial for planning and implementing secondary preventive interventions, as well as for stepping up efforts to address risk factors. Very few studies have discovered a connection between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and the onset and progression of DPN in T2DM. Objectives: The current study intends to investigate the relationship between ACE gene I/D polymorphism with T2DM and DPN subjects among the South Tamil Nadu regional population. Materials and Methods: Thirty T2DM patients with DPN, 30 T2DM patients without DPN, and 30 control (nondiabetic) subjects were enrolled in this study. DPN was diagnosed using clinical and neurophysiological evaluation. Blood samples were collected and subjected to relevant investigations including blood glucose, glycated hemoglobin, serum creatinine, and serum lipids. Polymerase chain reaction amplification was performed to genotype the DNA for ACE I/D polymorphism using specific primers. Results: The ACE genotypes were distributed as II, 17 (57%); DD, 3 (10%); and ID, 10 (33%) in control group; II, 7 (23%); DD, 11 (37%); and ID, 12 (40%) in T2DM without DPN group, II, 3 (10%); DD, 16 (53%); and ID, 11 (37%) in T2DM with DPN group. The frequency of DD genotype was significantly higher in T2DM (P = 0.03) and T2DM patients with DPN (P = 0.001) compared to controls. The DD genotype versus II genotype was found to be associated with an increased risk of DPN (odds ratio [OR] = 10.28; 95% confidence interval [CI] =2.55–41.37). The D allele was more frequent among T2DM patients with DPN (71.6%) followed by T2DM patients (56.6%) compared to controls (26.6%). The D allele (vs. the I allele) is associated with an increased risk of T2DM (OR = 3.59, 95% CI = 1.670–7.742) and DPN (OR = 6.95, 95% CI = 3.120–15.507). Conclusion: The D allele and DD genotype of the ACE gene may both be risk factors for T2DM; in fact, the D allele of this polymorphism may potentially be linked to the development of DPN in T2DM patients. This finding implies that it may be possible to prevent DPN by early detection by identifying defects in ACE I/D polymorphisms in the south Indian regional population.

PREDICTORS OF MAXIMUM STEP LENGTH IN OLDER ADULTS: ROLES FOR STRENGTH AND ACE GENOTYPE

Abstract Deficits in step length, assessed clinically by the maximum step length (MSL) test, are associated with poor balance and falls, in older adults. Determining predictors of MSL would facilitate targeted interventions to improve balance and reduce falls in older adults. Angiotensin-converting enzyme (ACE) insertion/deletion polymorphism genotypes interact with strength to predict stepping speed, but the interplay between ACE genotype, strength and MSL is unclear. Our objective was to determine whether strength and ACE DD genotype, through main effects or interactively, are associated with MSL, in older adults. Adults (N=103, female=58.2%, mean age 72.1 years, range 65-85 years) provided demographic, health and balance confidence information, completed grip strength and MSL testing, and provided saliva for genotyping. Multiple regression determined variance in MSL explained by strength, DD genotype (present/absent), and strength x genotype interaction, while controlling for covariates (age, sex, self-rated health and balance confidence). Covariates (model 1) explained 47.7% of MSL variance, while adding grip strength (model 2) explained additional 9.7% of variance. Adding DD genotype (model 3) explained .2%, while adding a strength x genotype interaction term (model 4) explained additional 3.4%, of MSL variance. The final model explained 61% of the variance in MSL (p<.001). DD genotype did not independently predict MSL (β=-.053; p=.421), but was interactively with strength, a significant predictor (β=.216; p=.005) of MSL. Strength was a significant predictor (β=.264; p=.003) of MSL, and as a modifiable physiological factor should be a focus of rehabilitation interventions to improve MSL and reduce falls risk in older adults.

Influence of the age factor and <i>АСЕ</i> and <i>PAI-1</i> gene polymorphism on the severity of the new coronavirus infection (SARS-CoV-2).

The paper investigates the role of the association of polymorphic variants of the tissue plasminogen activator inhibitor 1 (PAI-1) and angiotensin-converting enzyme (ACE) genes in 244 patients with coronavirus infection with varying degrees of disease severity (mild, moderate, and the group of deaths). The influence of the age factor in conjunction with various genotypes on the course of coronavirus infection is also being studied. An analysis of the frequencies of alleles and genotypes of ACE found statistically significant differences: the D allele is associated with the severity and outcome of COVID-19. The I/D genotype is associated with a milder course of the disease, while the D/D genotype increases the likelihood of death.

Correlation between the insertion-deletion variant of the angiotensin-converting enzyme gene and various classes of heart failure.

The angiotensin-converting enzyme (ACE) genetic variation for insertion/deletion (I/D) is located at the 16th intron of the ACE gene. A number of studies investigated the homozygous deletion genotype of ACE and its association with cardiovascular diseases. However, ACE's genetic variation and its association with heart failure (HF) is yet to be confirmed. We examined the possibility of the association between the ACE I/D gene variant with the severity of HF. The ACE genotypes were determined by polymerase chain reactions using samples derived from 150 patients with HF and 90 healthy subjects which were age and gender-matched. These patients included those of all four of the New York Heart Association (NYHA) classes. Echocardiography was performed on all HF patients and ejection fraction (EF), left ventricular systolic and diastolic diameters were measured. The HF patients were redistributed to systolic where EF is equal and less than 45% and non-systolic HF where EF is more than 45%. We demonstrate a statistically significant difference in DD genotype in NYHA class IV in comparison to the control group. The values of odds ratio (OR) (95%CI) of the DD genotype (DD vs ID and II) were 3.37 (1.01-11.19) (p value = 0.039) and the OR (95%CI) of the D allele (D vs I) was 2.55 (0.98-6.65) (p value = 0.049). Higher frequencies of D allele compared to I allele is linked to severity of HF. DD variant of the ACE gene is associated with NYHA class IV heart failure. This could have a profound impact on risk stratification and prognosis of HF in the management of this condition.

Association Between the Polymorphism of Angiotensin-Converting Enzyme Gene and Interleukin-1 Beta Gene and the Response to Erythropoietin Therapy in Dialysis Patients with Anemia.

The polymorphism of the angiotensin-converting enzyme (ACE) gene and interleukin-1 beta (IL-1b) gene could be associated with resistance in the treatment of anemia in dialysis patients with recombinant human erythropoietin (rHuEPO). The aim of the study was to evaluate the association between the polymorphism of the ACE and IL-1b genes and the response to rHuEPO therapy in dialysis patients with anemia. The study investigated 69 patients on dialysis with anemia treated with recombinant human erythropoietin for 12 months. Genotyping of ACE and IL-1b polymorphism was done in all study patients at the initiation of the study. The patient's demographic characteristics, dialysis vintage, and laboratory parameters were also evaluated as factors associated with rHuEPO resistance. The erythropoietin resistance index (ERI) was calculated as the weekly rHuEPO dose per kg of body weight, divided by the hemoglobin (Hb) concentration in g/dl. The Hb ≥ 110 g/l was registered in 37 (53.6%) patients. Patients with Hb ≥ 110 g/l were characterized by significantly higher serum levels of albumin, cholesterol, and iron than those with Hb < 110 g/l. The serum level of the CRP, the weekly dose of rHuEPO, and ERI were significantly higher in patients with Hb < 110 g/l compared to patients with Hb ≥ 110 g/l. The ERI value of ≥ 10 IUkg/weekly/g/dl was present in 27 (39.1%) patients. The serum levels of ferritin and CRP, and weekly dose of rHuEPO were significantly higher in patients with ERI value ≥ 10 IU kg/weekly/g/dl compared with the patients with ERI value < 10 IUkg/weekly/g/dl. There was no significant association between the ERI and polymorphism of the ACE and IL-1b genes in study patients. The polymorphism of the ACE and IL-1b genes was not significantly associated with the response to erythropoietin therapy in dialysis patients with anemia. Iron deficiency, malnutrition, and inflammation were factors associated with anemia and resistance to erythropoietin therapy in dialysis patients.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds.

The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m2) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO2), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. The results suggest that the association of the ACE gene with resting SaO2 is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.

Evaluating direct amplification from viral transport medium for SARS-CoV-2 detection, strain typing, and angiotensin-converting enzyme genotyping and expression assays.

The aim of this study was to compare the performance of direct amplification of viral nucleic acid from transport medium to extracted nucleic acid for polymerase chain reaction (PCR), sequencing, and genotyping applications. XpressAmp lysate and extracted total nucleic acid from viral transport medium containing nasopharyngeal specimens were evaluated across different molecular applications to determine performance characteristics. SARS-CoV-2 quantitative PCR and angiotensin-converting enzyme (ACE) genotyping assays worked well with XpressAmp lysate, almost equal with or better than extracted nucleic acid in some specimens. However, XpressAmp completely failed to perform in next-generation sequencing for strain typing. Both protocols failed to detect ACE2 expression in viral transport medium. Direct amplification of viral nucleic acid from viral transport medium containing nasopharyngeal specimen works well for molecular assays with low thresholds of quality; however, it does have limitations with assays that require high quality nucleic acid for input. Use of the XpressAmp protocol significantly improves turnaround time and allows for easy ramp-up of PCR and genotyping assays.

Association ofGenotype, High-G Tolerance, andBody Composition inJet Aircraft Aviators.

Pilots of high-performance F15 and F16 jets must undergo periodic assessment of +8.5 Gz tolerance in a centrifuge, which is classified as a high-intensity exercise. Prior research has indicated that exercise performance may be correlated with alpha-actinin3 (ACTN3) and angiotensin-converting enzyme (ACE) genes, frequently termed the sports genes. This study aimed to investigate how ACTN3 and ACE genotypes correlate with high-g tolerance of Korean F15 and F16 pilots. A total of 81 Korean F15 and F16 pilots (ages 25-39 years) volunteered to participate in human centrifuge testing at +8.5 Gz. Exercise tolerance was calculated as the mean breathing interval during high-g tests, the target gene genotypes (ACTN3 and ACE) were identified, and body composition measurements were measured. The relationship among the ACTN3 and ACE genotypes, high-g tolerance, and body compositions were evaluated. The ACTN3 genotypes identified included 23 RR (28.4%), 41 RX (50.6%), and 17 XX (21.0%). The ACE genotypes identified included 13 DD (16.0%), 39 DI (48.2%), and 29 II (35.8%). Both genes satisfied an equilibrium check. In multivariate analysis by Roy's max, the interaction of the target genes (ACTN3 and ACE) was significant (P < .05). The ACTN3 gene showed significance (P < .05), while ACE tended toward significance with a correlation of P = .057 with high-g tolerance(s). Body composition parameters including height, body weight, muscle mass, body mass index, body fat (%), and basal metabolic rate showed no significant correlation with either genotype. In a preliminary study, the RR ACTN3 genotype showed a significant correlation with +8.5 Gz tolerance. Pilots with the DI genotype showed the highest high-g tolerance in this test; however, the test pass rate was higher in pilots with the DD genotype in the preliminary study. This result shows the possibility of test passing and tolerance superiority consisting of two different factors in the relationship between high-g tolerance and ACE genotype. This study showed that pilots with the RR + DI genotype had the highest high-g tolerance, which correlated with the presence of the R and D alleles of the ACTN3 and ACE genes, respectively. However, body composition parameters were not significantly correlated with genotype. These results could suggest a plural gene effect on high-g tolerance; further follow-up is required to determine the practical usage and applications of these results.

ASSOCIATION OF ANGIOTENSIN-CONVERTING ENZYME I/D POLYMORPHISM AND HYPERTENSION AMONG YOUNG ADULTS: A PILOT STUDY FROM DELHI

Objective: Angiotensin converting enzyme (ACE) gene is a potent vasoconstrictor and directly involved in cell proliferation, differentiation, apoptosis and angiogenesis. Studies have reported that ACE gene activates the conversion of angiotensin I to angiotensin II and also inactive bradykinin. Bradykinin is a vasodilator which bring about its proteolysis which binds to the plasma membrane receptor and helps to produce the arteriolar constriction resulting in the rise of systolic and diastolic blood pressure. Blood pressure is additionally influenced by the interaction of genetic and other environmental factors, therefore this study tries to find an association between angiotensin-converting enzyme I/D polymorphism and hypertension among young adults Design and method: The present study was a cross sectional study conducted among young adults either sex from the age group of 18-30 living in Delhi, India. Standardized questionnaire was administered to collect data on demographic and physiological measurement. Overnight fasting intravenous blood of 5ml was collected on non-EDTA coated tube which were subjected to DNA extraction by salting out process (Miller, 1988). The extracted DNA was then aliquoted and amplified by allele-specific PCR followed by genotyping on 2% agarose gel (Rigat et al. 1990). The DNA was then screened for ACE I/D gene polymorphism. Statistical analysis was done using SPSS 2022 version. Results: The overall prevalence of hypertension in the given population was 25.3%. There was no significant difference in the distribution of ACE I/D genotypes wherein 17.4% of hypertensives were of the II genotype, 47% of ID genotype and 34.8% of the DD genotype. Conclusions: Although there was no significant association of ACE genotype with hypertension, which may be due to the small sample size but the significance of this study hints towards the importance of early detection and modifying lifestyle to improve overall health.of the individual as well as on the community level.

The effect of angiotensin converting enzyme gene insertion/deletion polymorphism on anthropometric and biochemical parameters among hypertension patients: A case-control study from Northwest Ethiopia.

The angiotensin-converting enzyme (ACE) gene polymorphism has recently been linked with altered anthropometric and biochemical parameters in hypertensive patients. However, these links are still poorly understood and there is scarce evidence on the topic. Therefore, this study aimed to assess the effect of ACE gene insertion/deletion (I/D) polymorphism on anthropometric and biochemical parameters among essential hypertension patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A case-control study with 64 cases and 64 controls was conducted from October 07, 2020, to June 02, 2021. The anthropometric measurements, biochemical parameters, and ACE gene polymorphism were determined using standard operating procedures, enzymatic colorimetric method, and polymerase chain reaction, respectively. A one-way analysis of variance was used to determine the association of genotypes with other study variables. P value < 0.05 was regarded as statistically significant. The systolic/diastolic blood pressure and blood glucose level (P-value<0.05) were significantly higher among study hypertensive patients with the DD genotype. However, anthropometric measures and lipid profiles of cases and controls were not associated with ACE gene polymorphism (P-value>0.05). The DD genotype of the ACE gene polymorphism was found to have a significant association with high blood pressure and blood glucose levels in the study population. Advanced studies with a considerable sample size may be needed to utilize the ACE genotype as a biomarker for the early detection of hypertension-related complications.

Ace gene insertion/deletion polymorphism is associated with glioblastoma in an Iranian population: a case-control study

Background. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has recently been reported to be associated with the pathogenesis and development of human cancers.This study aimed to assess the potential association between ACE (I/D) polymorphism and glioblastoma in an Iranian population.Material and Methods. This case-control study was conducted on 80 patients with glioblastoma and 80 healthy blood donors as controls. Gap-polymerase chain reaction (Gap-PCR) was used to determine the ACE (I/D) genotypes. PCR products were separated and measured by electrophoresis on a 2 % agarose gel.Results. Analysis of demographic data showed a significant difference in the family history of cancer between the case and control groups (p=0.03). The distribution of ACE gene variants including II, ID, and DD genotypes was also calculated, and significant differences were seen in the DD genotype (p=0.03) and D allele (p=0.04) between the glioblastoma cases and controls.Conclusion. ACE gene polymorphism was associated with glioblastoma in the study population. Further studies are needed to approve this finding.

Association polymorphism of guanine nucleotide-binding protein β3 subunit (GNB3) C825T and insertion/deletion of the angiotensin-converting enzyme (ACE) gene with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related heart disease. Genetic roles such as gene polymorphisms may relate to the etiology of PPCM. This study analyzes the association between single nucleotide gene polymorphism (SNP) guanine nucleotide-binding protein beta-3 subunit (GNB3) C825T and insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE) gene with the incidence of PPCM. An analytic observational study with a case-control design was conducted at the Integrated Cardiac Service Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. PPCM patients of the case and control groups were enrolled. Baseline characteristic data were collected and blood samples were analyzed for SNP in the GNB3 C825T gene and for I/D in the ACE gene by using the polymerase chain reaction, restriction fragment length polymorphism, and Sanger sequencing. We also assessed ACE levels among different ACE genotypes using a sandwich-ELISA test. A total of 100 patients were included in this study, with 34 PPCM cases and 66 controls. There were significant differences in GNB3 TT and TC genotypes in the case group compared with that in the control group (TT: 35.3% vs. 10.6%, p = 0.003; TC: 41.2% vs. 62.5%, p = 0.022). The TT genotype increased the risk of PPCM by 4.6-fold. There was also a significant difference in the ACE DD genotype in the case group compared with that in the control group (26.5% vs. 9.1%, p = 0.021). DD genotypes increased the risk of PPCM by 3.6-fold. ACE levels were significantly higher in the DD genotype group than in the ID and II genotype groups (4,356.88 ± 232.44 pg/mL vs. 3,980.91 ± 77.79 pg/mL vs. 3,679.94 ± 325.77 pg/mL, p < 0.001). The TT genotype of GNB3 and the DD genotype of the ACE are likely to increase the risk of PPCM. Therefore, these polymorphisms may be predisposing risk factors for PPCM incidence. ACE levels were significantly higher in the DD genotype group, which certainly had clinical implications for the management of PPCM patients in the administration of ACE inhibitors as one of the therapy options.

Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals.

Current research on the angiotensin-converting-enzyme (ACE) gene has yielded controversial results on whether different ACE polymorphisms are linked with human longevity. ACE polymorphisms are a risk factor for Alzheimer's disease and age-onset diseases that may contribute to the mortality of older people. Our goal is to consolidate existing studies, using artificial intelligence-assisted software to come to a more precise understanding of the role of the ACE gene in human longevity. The I (insertion) and D (deletion) polymorphisms in the intron are correlated with the levels of circulating ACE; homozygous D (DD) is high, and homozygous I (II) is low. Here, we performed a detailed meta-analysis of the I and D polymorphisms using centenarians (100+ years old), long-lived subjects (85+ years old), and control groups. ACE genotype distribution was analyzed across a total of 2054 centenarians and 12,074 controls, as well as 1367 long-lived subjects between the ages of 85-99, using the inverse variance and random effects methods. The ACE DD genotype was found to be favored in centenarians (OR: 1.41 (95% CI: 1.19-1.67), p < 0.0001) with a heterogeneity of 32%, and the II genotype slightly favored the control groups (OR: 0.81 (95% CI: 0.66-0.98), p = 0.03) with a heterogeneity of 28%, corroborating results from previous meta-analyses. Novel to our meta-analysis, the ID genotype was found to be favored in control groups (OR: 0.86 (95% CI: 0.76-0.97), p = 0.01) with a heterogeneity of 0%. The long-lived group showed a similar positive association between the DD genotype and longevity (OR: 1.34 (95% CI: 1.21-1.48), p < 0.0001) and a negative association between the II genotype and longevity (OR: 0.79 (95% CI: 0.70-0.88), p < 0.0001). The long-lived ID genotype did not show significant findings (OR: 0.93 (95% CI: 0.84-1.02), p = 0.79). In conclusion, the results suggest a significant positive association of the DD genotype with human longevity. However, despite the previous study, the results do not confirm a positive association of the ID genotype with human longevity. We suggest a few important paradoxical implications: (1) inhibition of ACE can increase longevity in model systems from nematodes to mammals, seemingly opposite to the finding in humans; (2) exceptional longevity associated with homozygous DD is also associated with age-related diseases with higher mortality risks in homozygous DD. We discuss ACE, longevity, and age-related diseases.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in patients with laryngeal cancer.

The aim of this study was to compare the distribution of the angiotensin-converting enzyme (ACE) I/D polymorphism between patients with laryngeal cancer (LC) and a control group and to examine the distribution of this polymorphism with clinical parameters related to LC. We enrolled 44 LC patients and 61 healthy controls. The ACE I/D polymorphism was genotyped with the PCR-RFLP method. The distribution of ACE genotypes (II, ID, and DD) and alleles (I or D) was evaluated with Pearson's chi-square test, and logistic regression analysis was performed for statistically significant parameters. There was no significant difference in ACE genotypes and alleles between LC patients and controls (p = 0.079 and p = 0.068, respectively). Among clinical parameters related to LC (extension of tumour, node metastasis, tumour stage and tumour location), only the presence of node metastasis was found to be significant in terms of ACE DD genotype (p = 0.137, p = 0.031, p = 0.147, p = 0.321 respectively). In the logistic regression analysis, the ACE DD genotype was increased 8.3 fold in nodal metastases. The findings of the study suggest that ACE genotypes and alleles do not affect the prevalence of LC, but the DD genotype of ACE polymorphism may increase the risk of lymph node metastasis in LC patients.