scholarly journals Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Elifcan Aladag ◽  
Zahit Tas ◽  
Bilgesu Safak Ozdemir ◽  
Tayfun Hilmi Akbaba ◽  
Meltem Gulsun Akpınar ◽  
...  

Introduction. The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. Results. The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001 ). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) ( p = 0.021 ). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. Conclusion. Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Hamid Ali-Bahar ◽  
Maysam Mard-Soltani ◽  
Yousef Paridar ◽  
Zahra Nasirbaghban ◽  
Zahra Sadat Hashemi ◽  
...  

Background: One of the major microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). Studies have shown that angiotensin-converting enzyme (ACE) gene polymorphisms are correlated with DR progression. Accordingly, the elucidation of the association between ACE gene polymorphism and the risk of DR development seems to be highly crucial. Methods: In this study, 195 individuals with type 2 diabetes mellitus (T2DM) were classified as the case group with retinopathy (99 people) and control group without retinopathy (96 people). Screening for DR was performed by ophthalmologists using clinical examination and fluorescein angiography. Different ACE genotypes (II, ID, and DD) were identified by the collection of blood samples, extraction of DNA, and PCR amplification using specific primers. Results: The frequency distribution of genotypes was significantly different between the case and control groups (P = 0.009). Interestingly, possessing a DD genotype made diabetic patients approximately 2.5 folds (95% CI = 1.271 - 4.840, P = 0.007) and 3.25 folds (95% CI = 1.312 - 8.051, P = 0.01) more susceptible to DR when compared to having DI and II genotypes, respectively. Moreover, having a D allele made diabetic individuals nearly 1.75 folds (95% CI = 1.167 - 2.623, P = 0.007) more susceptible to DR than possessing an I allele. Conclusions: Our results potentiate the hypothesis that the DD genotype and D allele of the ACE gene might play a role in the pathogenesis of DR.


2020 ◽  
Author(s):  
Vincent J. Manna ◽  
Salvatore J. Caradonna

ABSTRACTCoronavirus Disease 2019 (COVID-19) is transmitted through respiratory droplets containing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) particles. Once inhaled, SARS-CoV-2 particles gain entry into respiratory ciliated cells by interacting with angiotensin converting enzyme 2 (ACE2). It is known that ACE2 functions within the renin-angiotensin system to regulate blood pressure, fluid homeostasis and inflammation. However, it is largely unknown what roles ACE2 has in ciliated cells of the airway. Therefore, understanding the function and nature of ACE2 within airway tissue has become an essential element in combatting the COVID-19 pandemic. Airway mucociliary tissue was generated in-vitro using primary human nasal epithelial cells isolated from nasal turbinates of donors and the air-liquid interface (ALI) model of differentiation. Using ALI tissue we cloned transcripts for three distinct variants of ACE2, one of which encodes the full-length ACE2 protein, the other two transcripts are truncated isoforms that had only been predicted to exist via sequence analysis software. We demonstrate that all three isoforms have the capacity to be glycosylated, a known modification of full-length ACE2. Immunofluorescence microscopy of individual ACE2 isoform transfected cells reveals distinct localization of variant 1 relative to X1 and X2. Double staining immunohistochemistry of ALI tissue using antibodies to either the N-term or C-term region of ACE2 revealed distinct and overlapping signals in the apical cytosol of ciliated cells. Most notably only the ACE2 C-term antibody displayed plasma-membrane localization in ciliated cells. We also observed a decrease in the total amount of ACE2 in ALI tissue derived from a 33 year-old male donor when compared to a 34 year-old female donor, thus there may be variation in the abundance of ACE2 protein in the airway among the population. Together, our data begins to highlight the dynamic status of the ACE2 protein in airway mucociliary tissue and we propose multiple ACE2 parameters that may impact an individual’s susceptibility to SARS-CoV-2. These parameters include the balance of cytosolic versus membrane bound ACE2, isoform expression levels, maintenance of post-translational modifications and the impact of genetic, environmental and lifestyle factors on these processes.


2015 ◽  
Vol 38 (4) ◽  
pp. 164 ◽  
Author(s):  
Ahmet Bayar ◽  
Ali Turan ◽  
Kanat Gülle ◽  
Meryem Akpolat ◽  
İnci Turan ◽  
...  

Purpose: Angiotensin converting enzyme inhibitors (ACEI) and type I angiotensin receptor blockers (ARB) have been shown to exert significant effects on bone tissue via a local renin-angiotensin-aldosterone system (RAS). The aim of our study was to delineate their influences on fracture healing process. Methods: Sixty adult male Wistar Albino rats were divided into three groups. After undergoing surgical femoral fracture and fixation, the ACEI group received 10 mg/kg of Enalapril, the ARB group received 10 mg/kg of Losartan and the Control group did not receive any medication. Fracture healing was evaluated at second and fifth postoperative weeks by the Lane-Sandhu radiological staging system and by histological scoring system of Huoet al. ACE expression in fracture callus was studied by immunohistochemistry. Results: Both ACEI and ARB groups showed less fibrous tissue in the fracture area at the second week, but the histologic score differences were significant only between Control and ARB groups. At the fifth week, however, both radiological and histological scores for the ACEI group were significantly higher than both ARB and Control groups, while the scores for ARB and Control groups were similar. The presence of ACE expression in fracture callus was also observed. Conclusion: ACEIs had significant positive effects on fracture repair. Losartan failed to display these stimulatory effects, which suggests that local RAS in bone tissue exerts its actions via alternative receptors or pathways than the AT1 receptor.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
JENNIFER SHEARON ◽  
Rachel Fenner ◽  
Yulia Grigorova ◽  
Ross McDevitt ◽  
Samuel Ajamu ◽  
...  

Background: Aged Dahl salt sensitive rats (DSS) rats represent a model of vascular dementia, i.e., they develop central arterial stiffness (CAS), hypertension, and cognitive decline. DSS rats have compromised renin-angiotensin system (RAS) which is activated with age and contributes to hypertension. This study examined whether angiotensin converting enzyme (ACE) inhibitor, lisinopril, affects CAS and cognitive functions in aged male DSS (n=26). Methods & Results: Following initial measurements at 16-mo of age (baseline; BL), DSS were administered lisinopril through their water (LISI; 15mg/kg/day, n=11) or control treatment (n=15) for 2-mo. Pulse wave velocity (PWV), a marker of CAS, and systolic blood pressure (SBP) were measured at BL and at 18-mo of age. Open field test (OFT) to assess anxiety-like behavior and Morris water maze (MWM) to assess spatial memory were performed at 18-mo, then aortae and hearts were collected and weighed. Aortic wall collagen abundance was estimated by histochemistry. Statistical analyses were performed by 2-way ANOVA mixed effects model and t-test. The data are presented as mean ± SEM. At 18-mo of age, control animals had high SBP similar to BL (187±4 vs. 184±7 mmHg), while LISI-treated DSS had lower SBP by 39±4 mmHg vs. BL (p<0.01). PWV in control rats increased from 16 to 18-mo (7.0±0.6 vs. 10.8±1.0 m/s; p<0.05), while PWV in LISI-treated DSS decreased after 2-mo of treatment (7.1±0.3 vs. 5.4±0.3 m/s; p<0.01). Lower heart weights (2.9±0.1 vs. 3.7±0.3 g/kg BW; p<0.01), aortic weights (4.4±0.1 vs. 5.0±0.2 mg/mm/kg BW; p<0.01), and aortic medial collagen abundance (14.0±0.3 vs. 19.6±1.0 % of total; p<0.01) were observed in the LISI-treated rats vs. control rats. No differences between LISI-treated and control groups at 18-mo (38±10 vs. 25±6 cm traveled in center) were found in OFT. MWM results indicated that neither group at 18-mo of age was able to learn the task and therefore could not be accurately assessed for differences in spatial memory. Conclusion: Initiation of anti-hypertensive treatment in old age was effective in reducing aortic fibrosis and lowering SBP and PWV in DSS rats. Longer treatment may be needed to improve cognitive function in this model of vascular dementia. Supported by the NIH/NIA Intramural Research Program


2016 ◽  
Vol 35 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Fatimah Basil Al-Mukaynizi ◽  
Afrah AlKhuriji ◽  
Zaineb Babay ◽  
Mohammad Addar ◽  
Sooad AlDaihan ◽  
...  

Summary Background: An insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene has been associated with recurrent miscarriage (RM) in several populations. We initiated this study to determine the association, if any, between the I/D polymorphism of ACE gene and RM in Saudi females. Method: This study was conducted on 61 Saudi females suffering from RM (mean age: 34.1±6.2 years; range 15–45) attending clinics at King Khalid University Hospital, and 59 age matched females who had at least 2 children, as controls. Blood samples were drawn in EDTA tubes by venipuncture. DNA was extracted using the Puregene DNA purification kits. Insertion/Deletion (I/D) polymorphism of ACE gene was investigated by amplifying the genomic DNA by PCR using gene-specific primers. A single 190 bp or 490 bp band was obtained in the homozygous cases for the D allele or I allele, respectively, while the presence of both 190 and 490 bp bands indicated heterozygosity (ID). Statistical analysis: Deviation from Hardy-Weinberg equilibrium was determined (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). A standard chi-square (χ2) test was used for comparing the genotype and allele frequencies in the two groups and Students‘t’ test and χ2 test were employed to compare values between the two groups. P<0.05 was considered statistically significant. Results: The frequencies of DD, ID, and II genotypes were 56.7%, 29.5% and 4.9%, respectively, in females with RM and 54.2%, 42.3% and 3.3% respectively in the control group, but the difference was not statistically significant. Conclusion: In some populations, meta-analyses showed an association between I/D polymorphism and RM risk, and the D allele was implicated as an increased risk factor for RM. However, this association was not apparent in the Saudi females.


Author(s):  
V. Anand Kumar ◽  
J. Vijaya Shree

<p class="abstract"><strong>Background:</strong> This study aimed to evaluate the serum angiotensin converting enzyme (ACE) levels in patients with pemphigus vulgaris compared with healthy volunteers.</p><p class="abstract"><strong>Methods:</strong> In this study, 40 patients were selected in the study group with pemphigus vulgaris and 40 patients were selected in the control group i.e. healthy group. Serum ACE levels were determined by spectrophotometric method.<strong></strong></p><p class="abstract"><strong>Results:</strong> The mean ACE levels in study group and control group were 26.98±15.87 and 32.57±20.98 respectively. There was no statistically significant difference between both the groups (p=0.11). The mean ACE levels were 26.25±12.36 and 26.14±13.89 in females and males respectively in the study group which showed no significant difference (p=0.95). In the control group, the mean ACE levels were 26.22±19.77 and 38.54±11.11 in females and males respectively which showed a statistically significant difference (p=0.04). The mean ACE levels were higher in healthy males when compared to the males in the study group. The mean serum levels in females of both the groups were almost same.</p><p class="abstract"><strong>Conclusions:</strong> The serum ACE level was considerably lower in male study group i.e. pemphigus vulgaris patients compared with male control group i.e. healthy group, despite lack of any significant difference of serum ACE level between pemphigus and control group. Hence, ACE might have some relation with pemphigus vulgaris especially in male patients.</p>


2020 ◽  
Vol 16 (14) ◽  
pp. 1269-1275
Author(s):  
Sun-Wung Hsieh ◽  
Ming-Wei Liu ◽  
Ling-Chun Huang ◽  
Meng-Ni Wu ◽  
Yuan-Han Yang

Background: The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of β-amyloid (Aβ), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer`s Disease (AD) patients has yet to be elucidated. Objective: This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population. Method: The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI). Results: At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score. Conclusion: ACE gene is involved in aggravating BPSD among AD patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Simon B. Gressens ◽  
Georges Leftheriotis ◽  
Jean-Claude Dussaule ◽  
Martin Flamant ◽  
Bernard I. Levy ◽  
...  

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.


Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Heshmatollah Ghanbari ◽  
Alireza Dehghani ◽  
Awat Feizi ◽  
Arman Amirkhani ◽  
Mohsen Pourazizi

Purpose. To evaluate the serum level of angiotensin-converting enzyme (ACE) as an important component of the renin-angiotensin system (RAS) in optic neuritis (ON) compared to the healthy control group in the context investigating the possible role of ACE in ON pathogenesis. Methods. This case-control study was conducted on patients with ON and healthy controls. Serum ACE levels were assessed and compared between the two groups by using commercially available kits by ELISA for ACE. Results. Sixty-five ON patients (75.4% female, mean age 29.70 ± 8.30 years) and 65 controls (75.4% female, mean age 29.66 ± 8.36 years) were enrolled. The median serum ACE levels were 33.5 U/L (range: 25–540) and 26 U/L (range: 22.3–72) for the ON patients and controls, respectively. Serum ACE levels were significantly higher in the patients than in the control group (P<0.001). High level of serum ACE (defined as a serum ACE >65 U/L) was present in 9 (13.8%) patients with ON and 2 (3.1%) controls. Conclusion. Our results indicated that the serum level of ACE appeared to be significantly higher in acute ON than in normal controls.


2018 ◽  
Vol 15 (1) ◽  
pp. 151-155
Author(s):  
Narendra Mohan Verma ◽  
Arun Kumar Sah ◽  
Sanjeev Kumar Maurya

Chronic kidney disease (CKD) becomes a major problem for world health. Numerous studies have documented that the polymorphisms in angiotensin-converting enzyme (ACE) gene may contribute to an individual risk for the loss of kidney function. The present study was undertaken to evaluate the possible relationship between ACE G2350A gene polymorphism and the risk of CKD in Uttar Pradesh population. A total of 379 (159 CKD patients and 220 healthy controls) subjects were recruited for this study. All subjects were genotyped for G2350A polymorphism by PCR-RFLP method. The significant differences were reported between CKD patients and control groups in height, BMI, WC, WH ratio, SBP, DBP, FBS, serum creatinine, eGFR, triglyceride, total cholesterol, HDL and LDL (p < 0.05); while there was no difference in weight, WC, HC and VLDL. The frequency of AA genotype and A-allele were significantly higher in healthy controls than to patients. Conclusively, this study showed that the G2350A polymorphism may not contribute to CKD risk. Further investigations are warranted in larger sample size to confirm our results.


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