DD Genotype Research Articles

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.

Genetic Polymorphisms of ACE1 Rs4646994 Associated with Lung Cancer in Patients with Pulmonary Nodules: A Case-Control Study.

Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodules are eventually diagnosed as having benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule. This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, for which 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by the chi-square test, logistic regression analysis and cross analysis. The results showed that after adjusting for age and gender confounding factors, the risk of lung cancer in patients with pulmonary nodules carrying the DD genotype was more than three times that of the I carriers (II + ID) genotype (OR = 3.035, 95% CI, 1.252-7.356, p = 0.014). There was no significant difference between lung squamous cell carcinoma and lung adenocarcinoma in the polymorphism of ACE1 rs4646994 (p > 0.05). We also found that the ACE1 rs4646994 DD genotype frequency was inversely correlated with the risk of EGFR mutation in lung adenocarcinoma patients. Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

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.

Interactive associations of eczema with glutathione S-transferase genes in relation to autism spectrum disorder and its severity in Jamaican children

BackgroundComorbidity of eczema withith autism spectrum disorder (ASD) is increasing. We investigated the associations of eczema and its possible interaction with polymorphisms in glutathione S-transferase (GST) genes in relation to ASD and ASD severity. MethodUsing data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of eczema with GST genes in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domain-specific comparison scores (CSs) by fitting general linear models. ResultsAfter adjusting for child’s age and history of breastfeeding, eczema had no additive association with ASD [Matched Odds ratio (MOR) and 95 % Confidence Intervals (CI): 1.04 (0.76, 1.41), P = 0.82] or ASD severity (all P > 0.20). Using a recessive genetic model, eczema was significantly associated with ASD only among children with the Val/Val genotype for the GSTP1 Ile105Val polymorphism [MOR (95 % CI) = 2.04 (1.02, 4.08), P = 0.04, P for interaction = 0.03]. In addition, among ASD cases with the GSTM1 DD genotype, those with eczema had a marginally significant higher mean ADOS-2 Social Affect CS than those without eczema (7.3 vs. 6.8, P = 0.08, P for interaction = 0.09). ConclusionOur findings suggest children with certain genotypes for GST genes may be more susceptible for comorbidity of eczema and ASD, which is consistent with the role of GST genes in both conditions.

Association between ACE I/D genetic polymorphism and the severity of coronary artery disease in Vietnamese patients with acute myocardial infarction.

The severity of coronary artery disease is a prognostic factor for major adverse cardiovascular events in patients diagnosed with acute myocardial infarction. ACE I/D polymorphism is one of the genetic factors that may affect the severity of coronary artery disease. This study aimed to investigate the association between ACE I/D genotypes and the severity of coronary artery disease in patients with acute myocardial infarction. A single-center, prospective, observational study was conducted at the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital, Ho Chi Minh City, Vietnam from January 2020 to June 2021. All participants diagnosed with acute myocardial infarction underwent contrast-enhanced coronary angiography. The severity of coronary artery disease was determined by Gensini score. ACE I/D genotypes were identified in all subjects by using the polymerase chain reaction method. A total of 522 patients diagnosed with first acute myocardial infarction were recruited. The patients' median Gensini score was 34.3. The II, ID, and DD genotype rates of ACE I/D polymorphism were 48.9%, 36.4%, and 14.7%, respectively. After adjusting for confounding factors, multivariable linear regression analysis showed that the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotypes. The DD genotype of the ACE I/D polymorphism was associated with the severity of coronary artery disease in Vietnamese patients diagnosed with first acute myocardial infarction.

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.

Polymorphisms of the PLAG1 and their relationships with body measurements and carcass traits of Ongole crossbred cattle

Pleomorphic adenoma gene 1 (PLAG1) is a member of the PLAG family which is associated with body size in various cattle breeds. This study investigated the association of PLAG1 polymorphisms to carcass traits and body measurement of Ongole crossbred (PO) cattle in Kebumen. Chest girth, body length, body height, withers height, waist height, live body weight, carcass weight, and carcass percentage were carefully measured and recorded. The DNA genome extractions were originated from blood samples that was collected via jugular vein. The extracted DNA template used to amplify two PLAG1 polymorphisms target, namely, g.48308C>T and g.32212 (19 bp indel). Identification of g.48308C>T from PLAG1 was done via PCR-RFLP technique using SacII, wherein the 19 bp indel was obtained from PCR products. One-way analysis of variance and independent sample t-test were carried out to quantify the obtained data. This present study revealed variation in both g.48308C>T SNP and 19 bp indel. Three genotypes, TT, TC, and CC, were found for g.48308C>T SNP. Whilst two genotypes DD and DI genotypes were found for 19 bp indel. Non-significant differences were found between PLAG1 polymorphisms and traits of interest observed in Kebumen PO cattle population.

The ACE rs1799752 Variant Is Associated with COVID-19 Severity but Is Independent of Serum ACE Activity in Hospitalized and Recovered Patients.

This paper assesses the association of the insertion/deletion ACE (angiotensin-converting enzyme) variant (rs1799752 I/D) and the serum ACE activity with the severity of COVID-19 as well as its impact on post-COVID-19, and we compare these associations with those for patients with non-COVID-19 respiratory disorders. We studied 1252 patients with COVID-19, 104 subjects recovered from COVID-19, and 74 patients hospitalized with a respiratory disease different from COVID-19. The rs1799752 ACE variant was assessed using TaqMan® Assays. The serum ACE activity was determined using a colorimetric assay. The DD genotype was related to risk for invasive mechanical ventilation (IMV) requirement as an indicator of COVID-19 severity when compared to the frequencies of II + ID genotypes (p = 0.025, OR = 1.428, 95% CI = 1.046-1.949). In addition, this genotype was significantly higher in COVID-19 and post-COVID-19 groups than in the non-COVID-19 subjects. The serum ACE activity levels were lower in the COVID-19 group (22.30 U/L (13.84-32.23 U/L)), which was followed by the non-COVID-19 (27.94 U/L (20.32-53.36 U/L)) and post-COVID-19 subjects (50.00 U/L (42.16-62.25 U/L)). The DD genotype of the rs1799752 ACE variant was associated with the IMV requirement in patients with COVID-19, and low serum ACE activity levels could be related to patients with severe disease.

Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis. We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated. We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19. These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.

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.

Association between ACE and ACTN3 genes polymorphisms and athletic performance in elite and sub-elite Chinese youth male football players.

Previous studies have shown controversial relationships between ACE I/D and ACTN3 R577x polymorphisms and athletic performance. Therefore, the aim of this study was to assess athletic performance indicators of Chinese youth male football players with different ACE and ACTN3 gene profiles. This study recruited 73 elite (26 13-year-olds, 28 14-year-olds, and 19 15-year-olds) and 69 sub-elite (37 13-year-olds, 19 14-year-olds, and 13 15-year-olds) and 107 controls (63 13-year-olds, and 44 14-year olds aged 13-15 years, all participants were of Chinese Han origin. We measured height, body mass, thigh circumference, speed, explosive power, repeat sprints ability, and aerobic endurance in elite and sub-elite players. We used single nucleotide polymorphism technology to detect controls elite and sub-elite players' ACE and ACTN3 genotypes, Chi-squared (χ 2) tests were employed to test for Hardy-Weinberg equilibrium. χ 2 tests were also used to observe the association between the genotype distribution and allele frequencies between controls and elite and sub-elite players. The differences in parameters between the groups were analyzed using one-way analysis of variance and a Bonferroni's post-hoc test, with statistical significance set at p≤0.05. (1) The genotype distribution of the ACE I/D and ACTN3 R577x polymorphisms in controls, elite and sub-elite football players were consistent with Hardy-Weinberg equilibrium, except for the ACE genotype distribution of sub-elite players. (2) The RR and DD genotypes were significantly different between elite and sub-elite players (p = 0.024 and p = 0.02, respectively). (3) Elite players were more likely to have the RR genotype and less likely to have the DD genotype compared with sub-elite players. (4) Both elite and sub-elite RR players' Yo-yo intermittent recovery level 1 (YYIR1) running distance was significantly longer than that of RX players (p = 0.05 and p = 0.025, respectively). However, there was no significantly different in YYIR1 running distance between elite and sub-elite RR players. (5) Elite XX players' VO2 max was significantly higher than that of RX and sub-elite players. These results indicate that ACE I/D and ACTN3 R577x polymorphisms are not associated with muscle power in Chinese elite and sub-elite players. The XX genotype of ACTN3 is associated with the aerobic endurance of elite players.

Association of ACE ID, MTHFR C677T, and MIF-173GC variants with the clinical course of COVID-19 patients

The course of coronavirus disease-2019 (COVID-19) differs from person to person. The relationship between the genetic variations of the host and the course of COVID-19 has been a matter of interest. In this study, we investigated whether Angiotensin-Converting Enzyme (ACE) ID, Methylenetetrahydrofolate Reductase (MTHFR) C677T, and Macrophage Migration Inhibitory Factor (MIF)-173GC variants are risk factors for the clinical course of COVID-19 disease in Turkish patients. One hundred COVID-19 patients were included in the study. The diagnosis of COVID-19 was made using Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Chest Computed Tomography (CT). The patients were evaluated in 3 groups: intensive care, service, and outpatient treatment. ACE ID, MTHFR C677T, and MIF-173GC variants were genotyped by PCR-Restriction Fragment Length Polymorphism (RFLP) methods. When the genotype distribution between the groups was examined, it was found that the frequency of the ACE DD genotype and the D allele was higher in the intensive care group compared to the hospitalized and outpatient groups. MTHFR C677T CT genotype T allele and MIF-173GC, CC genotype C allele were more prevalent in the intensive care group compared to other groups. Patients with PCR-positive results had a higher MTHFR C677T C/C genotype and C allele. In CT-positive patients, the MTHFR C677T CT genotype and the MIF-173GC, G allele were more common. It is predicted that genetic predisposition may contribute to COVID-19 morbidity and mortality. Our results show that ACE ID, MTHFR C677T, and MIF-173GC variants affect the course of COVID-19 disease in the Turkish population.

Association of Plasminogen Activator Inhibitor-1 4G/5G and Angiotensin-Converting Enzyme I/D Polymorphisms with Recurrent Pregnancy Loss in Sudanese Women: A Case-Control study

The aim of our study was to investigate the relationship between the ACE I/D and PAI-1 4G/5G polymorphisms and RPL in Sudanese women. Methods and Results: A total of 232 people participated in this case-control study, including 119 women who had been diagnosed with RPL (Case group) and 113 healthy women (Control group). The case group (RPL) consisted of Sudanese women (mean age of 31.3+5.9 years) who had at least three unfavorable pregnancy outcomes. Women in the control group (Control) were matched by age (mean age of 30.3+5.4 years), had at least two healthy pregnancies, and had no history of unfavorable pregnancy outcomes or recurrent losses. Genomic DNA samples were isolated from the whole blood by using the GF-1 Blood DNA Extraction Kit (Vivantis Technologies Sdn. Bhd., Malaysia) according to the manufacturer`s protocol. The status of the PAI-1 4G/5G and ACE I/D polymorphism was determined by PCR. Analysis of the multiplicative and additive models for the ACE I/D polymorphism showed a significant risk of RPL with the carriage of the D allele (OR=2.07, 95% CI: 1.28-3.35, P=0.003) and the homozygous DD genotype (OR=2.40, 95% CI: 1.34-4.29, P=0.008). The multiplicative and additive models for the PAI-1 4G/5G polymorphism showed a significant risk of RPL with the carriage of the 4G allele (OR=3.11, 95% CI: 2.12-4.58, P=0.000) and the homozygous 4G/4G genotype (OR=3.09, 95% CI: 1.77-5.39, P=0.000). However, the carriage of risk-polymorphic markers, the ACE I/D and PAI-1 4G/5G polymorphisms, was not associated with the number of RPL. The combined carriage of the homozygous DD genotype and heterozygous ID genotype of the ACE I/D polymorphism with the homozygous 4G/4G genotype of the PAI-1 4G/5G polymorphism occurs significantly more often in RPL women than healthy women (P=0.000 and P=0.006, respectively). Carriage of the PAI-1 5G/5G genotype in healthy women was not associated with the ACE I/D polymorphism. Conclusion: Testing for the ACE I/D and PAI-1 4G/5G polymorphisms should be part of the standard examination for patients with RPL.

Clock 3111T/C and Period3 VNTR gene polymorphisms and proteins, and melatonin levels in women with infertility.

One of the causes of infertility is circadian rhythm disorders. This study aimed to investigate Clock 3111T/C and Period3 VNTR (variable number tandem repeat) gene polymorphisms and these gene proteins, some biochemical parameters, and circadian rhythm hormones in infertile women. Thirty-five infertile women and thirty-one healthy fertile women were included. Blood samples were taken in the mid-luteal phase. DNAs obtained from peripheral blood were analyzed using polymerase chain reaction-restriction fragment length polymorphism methods. Follicle-stimulating hormone, LH (luteinizing hormone), estradiol, prolactin, free triiodothyronine, fT4 (free thyroxine), thyroid-stimulating hormone, testosterone, cortisol, progesterone, prolactin, ferritin, vitamin B12, and folate levels in serum samples were determined by the electrochemiluminescence immunoassay method. Melatonin, Clock, and Period3 protein levels were determined with ELISA kits. There was a significant difference in the frequency of Period3 DD (Per34/4) genotype between the groups. The Clock protein level of the infertile group was higher than the fertile group. Clock protein levels of the fertile group were positively correlated with estradiol levels and negatively correlated with LH, prolactin, and fT4 levels. PER3 protein levels of the infertile group were negatively correlated with LH levels. Melatonin levels of the fertile group were positively correlated with progesterone levels and negatively correlated with cortisol levels. Melatonin levels of the infertile group were positively correlated with LH levels and negatively correlated with cortisol levels. Per34/4 genotype may be an independent risk factor in infertile women. Different correlation results found in fertile and infertile women can form the basis for future studies.

A genetic Study to Darwin's tubercle trait of External ear in the Population of Salah Al –Dein and Kirkuk

A genetic study for the trait of Darwin's tubercle in two ways : first , on a sample consisted of 52 family from Tikrit city in governorate Salah AL-Dein and 125 individual from their sons and 63 family from governorate of Kirkuk and 188 individual from their sons . Secondly , adoption of pedigree analysis method for seven families from governorate of Salah El-Dein and Kirkuk , which confirmed the darwin's tubercle trait is a genetic trait and the presence of tubercle is dominant absence . The results of Presence Darwin's tubercle also revealed different forms : Nodosity tubercle , Enlargement tubercle and Projection. The present study support the truth of single gene locus hypothesis for the inheritance of this trait , in spite of it record the presence of one offspring have darwin's tubercle between two parents do not have darwin's tubercle in one family. The results of the study distribution of phenotypic for the trait showed on a sample consisted of 1415 individual from the citizens of the governorate of Salah Al-Dein (920♂: 495♀) from the original samples (1446) , an elevated percentage of the presence tubercle among the males (99.2%) than the females (98.4%) . The percentage of presence tubercle in the whole population was (98.9%) . Concering the allelic frequency for the gene of darwin's tubercle, the D allele was observed a higher frequency than the d allele in the whole population of the governorate: 0.895, 0.105 for both of them respectively . Expected frequencies of the three genotypes of darwin's tubercle trait , revealed a prevalence of the homozygous (dominant) genotype DD over the homozygous (recessive) and heterozygous genotype in the population of the governorate: 0.801, 0.188, 0.011 for DD , Dd and dd respectively.

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.

Association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute myocardial infarction (AMI) remains a public health issue with high morbidity and mortality rates and significantly reduces patients' health-related quality of life. The identification of factors influencing coronary artery lesion characteristics in patients with AMI can contribute to the strategy of primary and secondary prevention for AMI. Purpose This study was aimed to investigate the ACE I/D genotype rate and its relationship with coronary artery lesion characteristics in AMI patients. Methods This study was conducted with the prospective cross-sectional method among AMI patients admitted to the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital from January 1, 2020 to June 30, 2021. The minimum sample size of this study was 163 patients. The ACE I/D genotype was determined at the Center for Molecular Biomedicine. Results During the study period, a total of 522 AMI patients were recruited at the Department of General Cardiology and Department of Interventional Cardiology. The mean age of the AMI patients was 63.9±11.7 and the age group 45-64 accounted for the most (46.4%). Males were predominant (71.5%). The patients' median Gensini score was 34.3. The II, ID and DD genotype rates of ACE I/D polymorphism were 48.9%, 36.4%, and 14.7% respectively. The ACE DD genotype was not associated with the location and number of diseased coronary arteries but was associated with the severity of coronary artery disease. Multivariable linear regression analysis showed that along with the Killip class, the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotype. Conclusions This has been the first study in Vietnam demonstrated the association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with AMI. The ACE I/D gene polymorphism may be considered for testing to contribute to the comprehensive assessment and aggressive treatment of AMI patients.

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

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

The Relation between ACE Gene Polymorphism and the Severity of COVID-19 Infection.

The coronavirus disease 2019 (COVID-19) pandemic, which emerged in China at the end of 2019, rapidly spread worldwide. The angiotensin-converting enzyme (ACE) gene contains an insertion/deletion (I/D) polymorphism that leads to a higher serum ACE level which is associated with several diseases and also with a high mortality rate in SARS. Therefore, this study aimed at assessing the association between ACE gene polymorphism and the risk and severity of COVID-19 disease in patients. Methodology. Forty-five SARS-CoV-2 infected patients and another random control group of 45 healthy individuals were included. The detection of ACE I/D gene polymorphism in both groups was done by PCR. 53% of infected patients with SARS-CoV-2 had an ACE deletion/deletion genotype (D/D), 27% had an ACE deletion/insertion genotype (D/I), and 20% had an ACE insertion/insertion genotype (I/I). On the one hand, the D/D variant was significantly detected in the COVID-19 patients compared to the control subjects, whereas the I/I variant was significantly detected in the control subjects compared to the COVID-19 patients (p = 0.004). The D/D variant subgroup showed the lowest lymphocytic count compared to the D/I or I/I subgroups. In addition, the C-reactive protein was significantly higher and the oxygen saturation was significantly lower in patients with the D/D allele compared to the other subgroups. ACE gene polymorphism, particularly the DD genotype, was observed to affect the severity of COVID-19 infection.