Angiotensin-converting Enzyme Gene Polymorphism Research Articles

Association between ACE gene polymorphisms and risk of suicide

Suicide is a health problem associated with a number of genetic factors. Genetics polymorphisms in several signaling pathways have been shown in the pathophysiology of suicidal behavior. Variants of the angiotensin converting enzyme (ACE) have been demonstrated to affect risk of some neuropsychiatric conditions and suicide attempt. In the current study, we assessed association between ACE rs4646994, rs1799752 and rs4359 polymorphisms and risk of suicide behavior in a population of Iranian patients attempted suicide (320 individuals who attempted suicide with soft methods and 230 suicide victims) and 300 healthy controls. Polymorphisms were genotyped using tetra-ARMS-PCR method. Data was analyzed using SPSS v.22.0. The rs4359 was associated with successful suicide under co-dominant model in a way that TC genotype was identified as a risk genotype (OR (95% CI)= 1.86 (1.26–2.75), P value=-0.02). In dominant model, TT+TC genotypes were associated with higher risk of successful suicide in comparison with CC genotype (OR (95% CI)= 1.71 (1.18–2.47), P value=-0.04). In over-dominant model, TT+CC genotypes were associated with lower risk in comparison with TC genotype (OR (95% CI)= 0.58 (0.41–0.83), P value=-0.03). rs1799752 was associated with higher risk of successful suicide under co-dominant, recessive and over-dominant models. In co-dominant model, while ID genotype increased the risk (OR (95% CI)= 2 (1.37–2.99), P value=0.003), II genotype decreased the risk (OR (95% CI)= 0.2 (0.09–0.45), P value<0.0001) in comparison with DD genotype). In recessive model, II genotype was associated with lower risk in comparison with total sum of the other genotypes (OR (95% CI)= 0.14 (0.07–0.28), P value<0.0001). The rs4646994 was not associated with risk of successful suicide. Besides, rs4359 was associated with risk of suicide attempt under over-dominant model in a way that TT+CC genotypes decreased risk of suicide attempt (OR (95% CI)= 0.67 (0.48–0.93), P value=0.04). rs1799752 was associated with risk of suicide attempt under co-dominant and recessive models in a way that II genotype conferred lower risk of suicide attempt (OR (95% CI)= 0.53 (0.34–0.83), P value=0.03). Finally, rs4646994 was associated with risk of suicide attempt in all models except for recessive model. I allele of this SNP increased risk of suicide attempt (OR (95% CI)= 1.47 (1.15–1.88), P value=0.018). Taken together, ACE1 gene can be considered as a risk locus for suicide behavior among Iranians.

Polymorphisms in the human angiotensin converting enzyme gene (ACE) linked to susceptibility of COVID-19 and malaria infections in the Ghanaian population

Genetic variations in the human angiotensin converting enzyme gene (ACE) influence ACE enzyme expression levels in humans and subsequently influence both communicable and non-communicable disease outcomes. More recently, polymorphisms in this gene have been linked to susceptibility and outcomes of infectious diseases such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and malaria infections. This study is the first to investigate the genetic diversity of ACE and ACE2 polymorphisms in the Ghanaian population. Archived filter blood blot samples from malaria patients aged ≤9 years were used. Molecular analysis for the detection of ACE rs4646994 (I/D), ACE2 rs2106809 (C/T) and rs2285666 (G/A) alleles as well as ACE2 exons 1–4 polymorphisms was conducted on 300 samples. The D allele (54%,162/300) was the most dominant polymorphism observed in the ACE rs4646994 gene whilst the G (68%, 204/300) and T alleles (59.3%,178/300) were the most frequent ACE2 rs2285666 and rs2106809 polymorphisms observed. For the 300 samples sequenced for ACE2 exons 1–4, analyses were done on 268, 282 and 137 quality sequences for exons 1, 2 and 3–4 respectively. For exon 1, the mutation D38N (2.2%; 6/268) was the most prevalent. The S19P and E37K mutations previously reported to influence COVID-19 infections were observed at low frequencies (0.4%, 1/268 each). No mutations were observed in exon 2. The N121K/T variants were the most seen in exons 3–4 at frequencies of 5.1% (K121, 7/137) and 2.9% (T121, 4/137) respectively. Most of the variants observed in the exons were novel compared to those reported in other populations in the world. This is the first study to investigate the genetic diversity of ACE and ACE2 genes in Ghanaians. The observation of novel mutations in the ACE2 gene is suggesting selection pressure. The importance of the mutations for communicable and non-communicable diseases (malaria and COVID-19) are further discussed.

Effect of insertion/deletion polymorphism of angiotensin-converting enzyme gene on efficacy of antihypertensive therapy with angiotensin II receptor blockers

The efficacy of the antihypertensive therapy may be related to genetic factors that can influence not only the degree of the blood pressure (BP) elevation but also contribute to the interindividual variability of response to the antihypertensive treatment.The aim of the work was to study pharmacodynamic parameters of the therapy efficacy with angiotensin II receptor blockers in the form of monotherapy and as part of combined drugs in patients with the arterial hypertension depending on the genetic features of patients – polymorphism of the gene encoding angiotensin-converting enzyme, or I/D-polymorphism.Materials and methods. The study included 179 patients of the Moscow region with a first-diagnosed arterial hypertension (AH) of 1–2 degree, including 141 (78.8%) women and 38 (21.2%) men aged from 32 to 69 years. By a simple randomization method, the patients were randomly allocated into groups receiving irbesartan and valsartan as mono- or combination therapy with hydrochlorthiazide. After 3 weeks of this pharmacotherapy, the presence of rs4646994 Alu Ins / Del genetic polymorphism of the angiotensin-converting enzyme (ACE) gene and the minimum equilibrium concentration of angiotensin II receptor blockers (ARBs) were determined.Results. The patients treated with irbesartan, the D/D genotype carriers, were significantly less likely to reach the target BP and more likely to require a pharmacotherapy intensification compared to I/D heterozygotes (p=0.042 and p=0.058, respectively) and I/I homozygotes (p=0.011 and p=0.011, respectively). The patients treated with valsartan, the D/D genotype carriers, significantly more often reached the target BP and significantly less often required a pharmacotherapy intensification than the I/D genotype carriers (p=0.05 and p=0.05, respectively). Herewith, at the end of the study, according to the results of the office BP measurements and daily BP monitoring, the target BP achievement was not significantly correlated with the I/D polymorphism of the ACE gene.Conclusion. When personalizing the AH therapy in patients of the Moscow region, the genotype I/I carriers by I/D polymorphism of the ACE gene, can be recommended irbesartan in the form of mono- or bicomponent therapy as a starting therapy of ARBs; the D/D genotype carriers can be recommended valsartan. A more pronounced decrease in the daytime systolic BP (SBP), the daytime diastolic BP (DBP) and the nighttime SBP variabilities in the valsartan group of patients, the D allele carriers may indicate a more persistent effect of the antihypertensive therapy.

The influence of the angiotensin-converting enzyme gene polymorphism and physical activity level on blood pressure and heart rate variability behavior

The influence of the angiotensin-converting enzyme gene polymorphism and physical activity level on blood pressure and heart rate variability behavior

The association of ACE gene polymorphism and serum ACE levels with diabetic nephropathy-a cross-sectional study

Diabetic nephropathy (DN) is the microvascular complication of type-2 diabetes that leads to end-stage renal disease. The angiotensin-converting enzyme gene that is a part of the renin-angiotensin-aldosterone system is considered one of the candidate genes responsible for the genetic predisposition of DN. To compare serum angiotensin converting enzyme (ACE) levels, the pattern of ACE gene polymorphism in patients with type-2 diabetes with or without nephropathy, to find the association between ACE gene polymorphism and various stages of DN, the association between serum ACE levels and various stages of DN. We enrolled 108 patients diagnosed with type-2 diabetes and 108 DN patients. Serum levels were estimated by ELISA and gene polymorphism was performed with gene sequencing. It was found that the serum ACE levels were higher in DN patients than in type-2 diabetics although the p-value was not significant. There was no significant association between serum ACE levels and various stages of nephropathy. The wild (GG genotype) distribution was more predominant in type-2 diabetic patients than in DN patients. There was a significant difference in the frequency of genotype with various stages of nephropathy and estimated glomerular filtration rate which was statistically significant (p = 0.0018). In summary, the study did not find a significant association between serum ACE levels and DN, nor did it observe a substantial impact of ACE gene polymorphism on serum ACE levels in DN patients. The findings also indicated that the ACE gene polymorphism might not have a direct influence on albuminuria stages. However, the wild-type genotype showed a trend toward protection against albuminuria development, while the carrier patients had a higher prevalence of severe albuminuria. Further research with larger sample sizes and longitudinal studies may provide deeper insights into the role of serum ACE levels and ACE gene polymorphism in the development and progression of DN.

The association of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients with diabetic nephropathy and essential hypertension

Objective — to establish possible associations of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. Clinical investigation and examinations involved 171 pts, from them 85 (49.7%) females and 86 (50.3%) males with DN of I—IV stages and EH of II—III stages, aged 31 to 82 years old (an average age was 59.38±1.58 years). They were also genotyped for rs4646994 (I/D) ACE and for rs1799983 (G894T) eNOS gene polymorphisms with the use of polymerase chain reaction. Among the patients with I/D polymorphism of ACE gene there were 24 (14.0%) pts with genotype II, 32 (18.7%) pts with genotype ID and 26 (15.2%) subjects with genotype DD. Among the participants with G894T eNOS gene polymorphism GG genotype was revealed in 29 (16.9%) pts, GT genotype was found in 33 (19.3%) cases and 27 (15.8%) examined persons had TT genotype. Standard parameters of lipid profile were measured in all included pts with a use of an immune enzyme method. Glucose oxidase and immune enzyme methods were used to define serum glucose and insulin levels; level of glycosylated hemoglobin (HbA1C) was detected by fluid chromatography method. Insulin resistance (IR) indices such as HOMA‑IR, triglyceride‑glucose index (TGGI), METS‑IR (metabolic score for insulin resistance) index were calculated by known formulas. Cardiometabolic risk (CMR) of the pts was estimated by ­METS‑IR index. Body mass index (BMI), body fat percentage (BFP), total fat mass (TFM) and fat mass index (FMI) in all the pts were calculated by standard known formulas. Serum uric acid concentration was measured with phosphovolframic method. Dapagliflozin 10 mg/daily was added for 24 weeks to the basic standard antidiabetic therapy including gliclazide or glimepiride and metformin combined with lipid lowering therapy containing atorvastatin. The standard therapy was not changed during the whole period of observation.&#x0D; Results. No association has been revealed between I/D ACE and G894T eNOS gene polymorphisms in pts with DN and EH, with a noted improvement of lipid blood spectrum due to administration of dapagliflozin in a dose of 10 mg/daily for 24 weeks. It has been established that allele D was associated with a reduction of dapagliflozin efficacy in the correction of carbohydrate metabolism disorders in pts with DN and EH. At presence of allele D (ID and DD) in genotype, the levels of glycemia, insulinemia, HbA1C, IR indices such as HOMA‑IR, TGGI, METS‑IR decreased less effective than in the case of allele D absence (genotype II). In pts with DN and EH who had G894T eNOS gene polymorphism, dapagliflozin 10 mg/daily improved muscle sensitivity to insulin and decreased CMR depended on genotype in the following order: GT &gt;TT &gt;GG, whereas the intensity of glycemia, insulinemia, HbA1C and HOMA‑IR index reduction was found to be associated with genotype as follows: GG &gt;GT &gt;TT. Allele I compared with allele D of I/D ACE gene polymorphism in pts with DN and EH was revealed to be associated with more significant reduction of BFP, TFM and FMI due to dapagliflozin administration. In pts with DN and EH who had G894T eNOS gene polymorphism dapagliflozin 10 mg/daily reduced a body mass due to its influence on fat accumulation but not on muscle tissue both in phenotype of visceral obesity (genotype GG) and in phenotype of sarcopenic obesity (genotype GT). In the realization of hypouricemic effects of dapagliflozin in patients with DN and EH, both genetic factors (D and T alleles of I/D ACE and G894T eNOS gene polymorphisms correspondingly), and metabolic factors (initial levels of HbA1C and UA together with anthropometric parameters characterized visceral obesity phenotype such as BMI, TFM and FMI) were involved.&#x0D; Conclusions. In pts with DN and EH, the association of I/D ACE (rs4646994) and G894T eNOS (rs1799983) gene polymorphisms with metabolic effects of dapagliflozin 10 mg/daily has been established. A presence of allele D of I/D ACE and allele T of G894T eNOS gene polymorphisms in genotype was concluded to be associated with less significant metabolic effects of dapagliflozin compared with an absence of these alleles in genotype.&#x0D;  

Association of insertion /deletion polymorphism of ace gene with essential hypertension in patients of Khyber Pakhtunkhwa.

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). 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. 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. 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.

Association between insertion/deletion polymorphism of the ace gene with risk of hypertension

This study conducted an initial investigation into the association between ACE gene insertion/deletion (I/D) polymorphisms (rs1799752) and hypertension in the Republic of Srpska, Bosnia and Herzegovina. The study featured two distinct groups, each with 100 subjects, systematically categorized based on hypertension status and gender. DNA was extracted, PCR-amplified, and analyzed by gel electrophoresis. Results revealed a higher prevalence of the DD genotype and the D allele in the hypertensive group, although statistical significance was not observed. The II genotype occurred in 18% of the hypertension group and 21% in the control group. A significant difference was found in allele I frequencies between the two groups (p=0.004), with no gender-related variations in ACE alleles. The limited sample size may have constrained the ability to detect statistically significant differences. The odds ratio for the (DD + ID) genotype compared to II was 1.2110 (95% CI: 0.6006 to 2.4418; p=0.5927), indicating no statistical significance. Furthermore, no significant associations were identified between ACE genotypes and alleles and gender. In summary, this preliminary study suggests a potential trend towards a higher prevalence of the ACE gene D allele and DD genotype in hypertensive individuals. However, due to the small sample size, these associations did not achieve statistical significance in this population. Larger-scale investigations are needed for more definitive insights into the relationship between ACE gene polymorphisms and hypertension.

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.

Role of Insertion/Deletion Polymorphism for Angiotensin Converting Enzyme Gene in Hypertension

Insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene is a key component of the Renin-Angiotensin-Aldosterone System (RAAS). It has been proposed as an independent factor for hypertension and other cardiovascular diseases. Consequently, it has been extensively studied in various populations. The aim of this study is to investigate I/D polymorphism of ACE gene and its connection to hypertension in population of Tuzla Canton (Bosnia &amp; Herzegovina). The study included 60 hypertensive subjects and 60 healthy control subjects with no risk factors for hypertension. I/D polymorphism was genotyped by polymerase chain reaction followed by gel electrophoresis and data obtained were statistically analysed using Chi square test. Odd’s ratios were calculated with a 95% confidence interval. P-value &lt; 0.05 was considered significant. Odd’s ratios were calculated with a 95% confidence interval. P-value &lt;0.05 was considered significant. Higher frequency of genotype D/D and allele D was determined in subjects with hypertension compared to control subjects but there is no statistical significance (p&gt;0.05). However, statistically significant association was found in compared groups of subjects with genotypes DD + ID, in regards to genotype I/I (p&lt;0.05). The results indicate the conclusion that ACE I/D polymorphism cannot be considered the main risk factor for development of hypertension, but its influence should be investigated together with other genetic and acquired risk factors that are associated with hypertension. This research contributes to the on-going exploration of molecular-genetic associations with hypertension.

Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome.

Long COVID-19 syndrome is present in 5-10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infectionA total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility. The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521-8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785-6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19.

Genotype AA of ACE2 G8790A (rs2285666) Has Protective Potential Against COVID-19 Disease Severity

Background: SARS-CoV-2 virus uses angiotensin converting enzyme 2 (ACE2), a key enzyme of the renin angiotensin system (RAS) as the functional receptor for cell fusion and induction of infections in the respiratory system. Functional ACE2 gene polymorphisms may lead to RAS imbalance and are associated with COVID-19 susceptibility and severity. ACE2 G8790A (rs2285666), a splice region variant, is well characterized in various populations across the world. In the present study, the role of ACE2 G8790A (rs2285666) variant as risk predictor for severity of COVID-19 infection was investigated.Materials and methods: One-hundred COVID-19 subjects were included in the study and divided into: subjects with a history of severe infection and ICU-admitted (Group 1) and subjects with mild to moderate COVID-19 infection (Group 2). Genotype analysis for rs2285666 of ACE2 was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.Results: The distribution of ACE2 G8790A (rs2285666) genotypes were GG 62%, GA 18%, and AA 20% in Group 1 and GG 34%, GA 14%, and AA 52% in Group 2, respectively. The A allele of rs2285666 (p≤0.001; OR=3.4; 95% CI=1.89–6.107) were less frequent in Group 1 as compared to Group 2. Also, a statistically significant difference was found between severity of COVID-19 infection with age and comorbidities such as diabetes, hypertension, chronic kidney disease, but not gender.Conclusion: Our findings suggest the possibility of a protective mechanism of the AA genotype of ACE2 G8790A (rs2285666) variant against COVID-19 disease severity.Keywords: COVID-19, ACE2 gene, renin-angiotensin system, genetic association, rs2285666, sanger sequencing

Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients

Despite remarkable discoveries in the genetic susceptibility of coronary artery disease (CAD), a large part of heritability awaits identification. Epistasis or gene‐gene interaction has a profound influence on CAD and might contribute to its missed genetic variability; however, this impact was largely unexplored. Here, we appraised the associations of gene-gene interactions and haplotypes of five polymorphisms, namely methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), apolipoprotein B (APOB) R3500Q, and apolipoprotein E (APOE) ε4 with the risk of myocardial infarction (MI) and unstable angina (UA). Gene-environment interactions with traditional risk factors and clinical data were also scrutinized. This study recruited 100 MI, 50 UA patients, and 100 apparently healthy controls. Logistic regression models were employed in association analyses. We remarked that the single locus effect of individual polymorphisms was relatively weak; however, a magnified effect of their combination via gene-gene interaction may predict MI risk after adjustment for multiple comparisons. Only MTHFR C677T, ACE I/D, and APOB R5300Q were associated with the risk of UA, and the ACE I/D-R3500Q interaction posed a decreased UA risk. APOB R3500Q was in strong linkage disequilibrium with MTHFR C677T, ACE I/D, and APE ε4 polymorphisms. The TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes were associated with escalating MI risk, while the CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk compared to controls. Interestingly, the CADGε4 and CAIGε3 haplotypes were strongly associated with the presence of diabetes and hypertension, respectively in MI patients; both haplotypes stratified patients according to the ECHO results. In UA, the CDG haplotype was negatively associated with the presence of diabetes or dilated heart. Conclusively, our results advocate that a stronger combined effect of polymorphisms in MTHFR, ACE, APOB, and APOE genes via gene-gene and gene-environment interactions might help in risk stratification of MI and UA patients.

ACE and AT2R1 gene polymorphism in patients with chronic vascular encephalopathy: association with neuroimaging changes and cognitive functioning

Background. Given the synergistic effect of the ACE and AT2R1 genes and their impact on the maintenance of homeostatic processes, the aim of our research was to identify the associations of the studied polymorphic variants of the ACE and AT2R1 genes with neuroimaging changes, data from arterial duplex ultrasound and cognitive functioning in patients with chronic vascular encephalopathy (CVE). Materials and methods. A retrospective analysis of 145 medical records of patients with CVE was conducted, of which 18 patients underwent a molecular genetic study. The control group consisted of 12 people representative in terms of age and gender. Neuroimaging was performed using multislice computed tomography or magnetic resonance imaging. The state of cerebral blood flow was studied using transcranial duplex ultrasound of intracranial and extracranial vessels. The cognitive functioning was tested using the Montreal Cognitive Assessment. Results. When analyzing the associations of polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene with neuroimaging changes and parameters of cerebral hemodynamics in CVE among carriers of I and D alleles of the ACE gene, a probable relationship was found between their frequency distribution and the presence/absence of gliosis phenomena (62.69 % of D allele carriers were diagnosed with gliosis, p &lt; 0.05); a probable relationship between the frequency distribution of the D/D genotype of the ACE gene and the presence of angiospasm (in 72.73 % of patients), insufficiency of blood flow in the carotid system (72.73 % of cases) and vertebrobasilar insufficiency (in 36.36 % of people). When evaluating the dependence of cognitive functions based on the Montreal Cognitive Assessment score in patients with CVE on the polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene, probable changes were revealed in the frequency distribution of genotypes and alleles of the polymorphic I/D variant of the ACE gene (χ2 = 11.33; p = 0.023), while all carriers of the D/D genotype have impaired cognitive functioning (moderate in 36.36 % and mild in 63.64 % of cases), which also corresponds to the frequency of the D allele distribution in this cohort of patients (29.63 % of people have a moderate cognitive impairment and 70.37 % — a mild cognitive impairment, p = 0.013). Conclusions. The study results indicate that the ACE gene may be involved in the development of neuroimaging changes and cognitive decline in CVE.

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.

Association of ACE gene polymorphism with atherosclerosis progression and duration of independent living in the elderly

Association of ACE gene polymorphism with atherosclerosis progression and duration of independent living in the elderly

ACE Gene I/D Polymorphism and Cardiometabolic Risk Factors: A Cross Sectional Study of Rural Population.

The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population.

Assessment of the association of ACE gene polymorphism with acute coronary syndrome in patients after a coronavirus disease 2019

Aim. To evaluate the association of the nucleotide sequence variant rs1799752 (I/D) of the angiotensin-converting enzyme (ACE) gene with acute coronary syndrome (ACS) in patients after a coronavirus disease 2019 (COVID-19).Material and methods. The study included 100 patients (women — 50, men — 50) with ACS and prior COVID-19, verified by a polymerase chain reaction (PCR), hospitalized in the regional vascular center № 7 of the City Clinical Hospital № 2 city of Novosibirsk. The mean age of women and men was 59,5±7,2 years and 53,5±9,3 years, respectively. The diagnosis of ACS was established according to a set of criteria proposed and established by the Russian Society of Cardiology and in accordance with the updated 2020 guidelines. Patients underwent examinations, coronary angiography with stenting, as provided for in the standards of care and guidelines. In patients, the nucleotide sequence variant rs1799752 of the ACE gene was determined using PCR. The comparison group consisted of 200 patients with ACS without COVID-19 (no positive PCR or antibodies). Statistical analysis was carried out using the SPSS 17.0.5 software package.Results. When comparing the frequencies of rs1799752 genotypes of the ACE gene in groups with ACS with COVID-19 and ACS without COVID-19, significant differences were obtained (p=0,013). In the group with ACS and COVID-19, carriage of the heterozygous genotype was less common (p=0,005) and there was an accumulation of carriers of the homozygous DD genotype (1,6 times higher; 26% vs 16%; p=0,044).Conclusion. The nucleotide sequence variant rs1799752 (I/D) of the ACE gene is associated with ACS in patients after COVID-19.

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

Cancer patients with Angiotensin-converting enzyme (ACE) gene polymorphism and COVID-19 phenotypic expression predisposed to SARS-CoV-2 infection

Pathogenesis of COVID-19 has been linked to the Angiotensin system. Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus, serves as a cellular receptor for SARS-CoV-2, suggesting that a person's vulnerability to infection may be controlled by how much of the ACE2 gene is expressed. It is also possible that the severity of COVID-19 is related to the equilibrium between ACE1 and ACE2 activity, which has been linked to the etiology of respiratory disorders. This study aimed to investigate the association of ACE1 I/D polymorphism with the severity of Covid-19. The study looked at 113 people-(50 healthy controls, 63 people with Covid). Results for the ACE2 rs4240157 T &gt; C polymorphism were obtained. Logistic regression was used to evaluate the distribution frequencies of variables across the study groups. The ACE1-CC*CT genotype (p = 0.049) and male gender (p0.001) were related to severe COVID-19. COVID-19 severity was found to be associated with the ACE2–CT genotype through multiple logistic regression under the co-dominant inheritance model: CC*CT Allele, 95% CI (0.0104 to 0.2954), Significance level, (0.0007) Odd Ratio (0.0556); CC*TT Allele, 95% CI (0.1854 to 6.1927), Significance level, (0.9386) Odd Ratio (1.0714); and CT*TT (19.2857). This was assuming the ACE2–CC*CT genotype was connected with covid-19 severity. However, the ACE2 polymorphism did not affect the development of illness. In conclusion, male gender, malignancy, and the ACE1 genotype were linked to a negative result of COVID-19. Our results indicated that ACE1-C/T might affect COVID-19 severity; however, this association was hypertensive status-specific. However, this finding needs to be confirmed in additional large samples.