Angiotensin-converting Enzyme Allele Research Articles

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

ObjectiveThe aim of this study was to examine angiotensin converting enzyme (ACE) insertion/deletion, alpha adducin, and interleukin-10 (IL-10) gene polymorphisms (GPs) in terms of both idiopathic sudden sensorineural hearing loss (ISSNHL) risk and their potential prognostic effects. MethodsThe study group consisted of 70 patients and the control group consisted of 50 patients. Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction. Age, sex, affected side, tinnitus, and vertiginous symptom status, number of days between symptom onset and hospital admission, pure tone audiometry results at admission and after treatment were included in the study. Data were compared statistically. ResultsThe D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group (p = 0.032). II genotype was associated with a reduced risk of ISSNHL (p = 0.036). The amount of hearing loss was significantly higher in patients with the TT genotype (p = 0.027) and T allele of the IL-10 GP (p = 0.035) than in the patients without this allele. Severe hearing loss was a poor prognostic factor (p = 0.008). ConclusionsThe D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology. Due to the association of this allele with occlusive vascular pathologies, ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.

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.

Genetic Polymorphism of the Angiotensin-Converting Enzyme in Bronchial Asthma

Background: Bronchial asthma (BA) is among the most prevalent chronic inflammatory disorders of the lung airways, and it has become clear that a combination of genetic predisposition and environmental factors plays a critical role in its pathogenesis. Objective: The correlation of the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and other factors with risk for bronchial asthma development was assessed. Materials and Methods: Online literature search was conducted to identify the most relevant studies. Results and Discussion: The ACE insertion/deletion (I/D) gene polymorphism, correlating with cellular and circulating ACE concentration, may play a critical role in BA pathogenesis and has been a focus of numerous epidemiologic studies; however, the results are currently inconclusive. The contradictions in the literature between research groups on the role of ACE alleles and genotypes can be explained by genetic variation and multifactorial causes of BA. Conclusion: This literature review demonstrates that the ACE I/D polymorphism might be related to the risk of bronchial asthma and can become a useful tool in designing effective treatment approaches. Bangladesh Journal of Medical Science Vol. 21 No. 03 July’22 Page: 492-501

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis

Background and aimsThe association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region). Material and methodsOur data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression. ResultsOf 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33–2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27–3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54–3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78–6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07–2.88; p = 0.024). ConclusionOur result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.

Association of laboratory parameters and genetic polymorphisms with ischemic stroke in Chinese Han population.

Numerous genetic polymorphisms and clinical laboratory parameters are associated with ischemic stroke (IS). However, the results of such studies have frequently been inconsistent. The aim of the present study was to evaluate associations between clinical laboratory parameters with genetic polymorphisms that influence the risk of IS in a Chinese Han population. Clinical laboratory parameters were measured by an automatic biochemical analyzer. Genotype and allele frequencies of the polymorphisms angiotensin-converting enzyme (ACE) D/I, methylene tetrahydrofolate reductase (MTHFR) C677T and β-fibrinogen (β-Fg) A/G, 455/148T/C were characterized by restriction fragment length polymorphism-PCR. Furthermore, the gene polymorphisms plasminogen activator inhibitor (PAI)-1-4G/5G and apolipoprotein E (ApoE) ε2,3,4 were characterized by allele-specific PCR. The associations of genotype and allele frequencies of the six risk genes in different groups with clinical laboratory parameters were analyzed by chi-square tests. The distribution maps of the polymorphisms of the six genes and clinical laboratory parameters were compared between a control group of 336 healthy individuals and 762 patients with IS. Certain laboratory parameters were associated with ACE I/D, β-Fg-455 A/G and PAI-1 4G/5G. The D allele of ACE I/D was associated with high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). Furthermore, high levels of fasting blood glucose, triglyceride and LDL-C were risk factors for IS. There were significant differences in the genotype frequencies of ACE I/D, β-Fg-455 A/G and β-Fg-148 T/C between the IS and the control group. In conclusion, clinical laboratory parameters were associated with the risk of polymorphisms of IS-related genes. The present results support the determination of a range of control values of clinical laboratory parameters for common genotypes in patients with diabetes and hyperlipidemia as a strategy for the early prevention of IS.

Angiotensin-converting enzyme (ACE) insertion/deletion gene polymorphism across ethnicity: a narrative review of performance gene

Angiotensin-converting enzyme (ACE) gene has been reported to be one of the candidate genes for endurance performance. The ACE gene insertion/deletion (I/D) polymorphism (rs4646994) is responsible for the variation in the ACE plasma level. The insertion (I allele) of ACE I/D gene polymorphism decreases the level of ACE plasma, thus reducing skeletal muscle vasoconstriction. Skeletal muscle vasoconstriction increases oxygenated blood supply to working muscles for endurance performance. On the other hand, the D allele of ACE I/D gene polymorphism increases the level of ACE plasma, leading to skeletal muscle hypertrophy. Therefore, the D allele may be helpful for strength or power performance. However, evidence for the involvement of these alleles in improving endurance performance and muscle strength is inconsistent and warrants further studies. These inconsistencies may be attributed to the small sample size and the potential causes of the racial and ethnic differences used in the previous studies. Therefore, this brief review reported a summary of the current literature on the association of the ACE I/D gene polymorphism on human physical performance across populations. The findings of this review may serve as a reliable platform and guidance for future research to provide a better understanding of the potential role of this variant on human physical performance concerning ethnicity.

Geographical ancestry affects normal hemoglobin values in high-altitude residents.

Increasing the hemoglobin (Hb) concentration is a major mechanism adjusting arterial oxygen content to decreased oxygen partial pressure of inspired air at high altitude. Approximately 5% of the world's population living at altitudes higher than 1,500 m shows this adaptive mechanism. Notably, there is a wide variation in the extent of increase in Hb concentration among different populations. This short review summarizes available information on Hb concentrations of high-altitude residents living at comparable altitudes (3,500-4,500 m) in different regions of the world. An increased Hb concentration is found in all high-altitude populations. The highest mean Hb concentration was found in adult male Andean residents and in Han Chinese living at high altitude, whereas it was lowest in Ethiopians, Tibetans, and Sherpas. A lower plasma volume in Andean high-altitude natives may offer a partial explanation. Indeed, male Andean high-altitude natives have a lower plasma volume than Tibetans and Ethiopians. Moreover, Hb values were lower in adult, nonpregnant females than in males; differences between populations of different ancestry were less pronounced. Various genetic polymorphisms were detected in high-altitude residents thought to favor life in a hypoxic environment, some of which correlate with the relatively low Hb concentration in the Tibetans and Ethiopians, whereas differences in angiotensin-converting enzyme allele distribution may be related to elevated Hb in the Andeans. Taken together, these results indicate different sensitivity of oxygen dependent control of erythropoiesis or plasma volume among populations of different geographical ancestry, offering explanations for differences in the Hb concentration at high altitude.

Effects of genetic variability on running performance in professional runners

Introduction: With the recent advancement in the field of genetics, researchers and general public are interested to know the effects of genetic variability on human body. A variety of studies can be found literature regarding the genetic variabilities on human body, however, there is a scarcity of data regarding systematic review on the topic. This review was conducted in order to systematically review the available literature on the effects of genetic variability on running performance in professional runners. Material & Methods: A systematic review was conducted according to PRISMA guidelines. The literature search was performed in different databases using the terms genes OR genetic (variation, variability, polymorphism) OR genomics AND running (performance, status, success) OR elite runners OR competitive running. Research articles published in English language from inception of medical literature to August 2019 that reported the effects of genetic variability on running performance were included. Those studies were excluded which reported association of gene mutations with genetic disorders. Reviews, commentaries, letter to editors and conference papers were excluded. Results: Out of total 8 included studies, 5 were case control and 3 were cohort studies. Six articles showed association between genetic variability and running performance while 2 reported no association between genetic variability and running performance in professional runners. Three studies investigated 'I' and 'D' allele of angiotensin-converting enzyme (ACE) gene, out of which two studies found association between 'D' allele of 'ACE' gene and running performance. Besides ACE, the included studies reported association between running performance and 'C' allele of aquaporin 1, Pro582 C allele of rs11549465 & 'A' allele of rs17099207 of HIF1A gene, bradykinin receptor B2, adrenergic receptor beta 2 & adenosine monophosphate deaminase 1 and Titin gene. Conclusion: Genes such as 'ACE', 'HIF1A', aquaporin '1' and Titin may be associated with running performance in professional runners, however, there is limited evidence regarding it as only few articles have been published on this topic. Majority of the published articles are case control studies which clearly indicate a demand for conducting high quality research in this area.

The Effect of Angiotensin-Converting Enzyme Gene Polymorphisms on the Clinical Efficacy of Perindopril Prescribed for Acute Myocardial Infarction in Chinese Han Patients.

Objective: Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that is commonly used in the treatment of Chinese Han patients with acute myocardial infarction (AMI). However, there have been few studies on whether polymorphisms of the ACE gene affect the efficacy of perindopril or the prognosis of AMI patients. The purpose of this study was to analyze the relationship among the ACE rs121912703 (C>T), rs767880620 (C>A), and rs397514689 (C>T) gene polymorphisms and the prognosis of AMI patients and the clinical efficacy of perindopril in the treatment of AMI. Methods: The ACE genotypes at the rs121912703, rs767880620, and rs397514689 loci in 225 AMI patients treated with perindopril were determined by polymerase chain reaction/Sanger sequencing. Differences in cardiac structure, functional indicators, hemodynamic parameters, and related laboratory indicators were detected before and after treatment. Results: After administration of perindopril, improved ventricular remodeling in AMI patients with wild-type ACE was better than in patients with the ACE rs121912703, rs767880620, and rs397514689 minor variant alleles. The patients harboring wild-type ACE had lower systolic blood pressure and diastolic blood pressure than the patients harboring the minor variant alleles (p < 0.01). The contents of serum ACE and Ang II (angiotensin II) in AMI patients carrying the wild-type ACE alleles were lower than those of patients harboring any of the minor variant alleles (p < 0.01). The 3-year survival time of AMI patients carrying the wild-type ACE alleles was markedly greater compared with AMI patients carrying the mutant genes (p < 0.01). Conclusion: Mutations at the ACE rs121912703, rs767880620, and rs397514689 loci affect the efficacy of perindopril on ventricular remodeling and hemodynamics in Chinese Han AMI patients. The 3-year survival of AMI patients harboring the variant alleles is less than that of the patients harboring the wild-type gene.

ACE Gene Plays a Key Role in Reducing Blood Pressure in The Hyperintensive Elderly After Resistance Training.

Montrezol, FT, Marinho, R, Mota, GdFAd, D'almeida, V, de Oliveira, EM, Gomes, RJ, and Medeiros, A. ACE gene plays a key role in reducing blood pressure in the hyperintensive elderly after resistance training. J Strength Cond Res 33(4): 1119-1129, 2019-Hypertension is a difficult disease to control and exercise training plays a key role in hypertension control. Some individuals are not responsive to exercise training; so, we highlight the polymorphism of I allele of angiotensin-converting enzyme (ACE) as a factor responsible for this lack of responsiveness. The aim of this study was to evaluate the influence of ACE insertion/deletion genotypes on effects of resistance training on blood pressure (BP) and chronic inflammation. Eighty-six hypertensive volunteers, aged between 60 and 80, were evaluated. They performed 16 weeks of resistance training at 50% of 1 maximal repetition. The greatest benefits were seen on homozygous of the Insertion allele, whom presented reduction of systolic blood pressure (SBP: 129.31 ± 13.34 vs. 122.56 ± 9.68 mm Hg, p < 0.001) and diastolic blood pressure (DBP: 79.18 ± 8.05 vs. 70.12 ± 7.71 mm Hg, p < 0.01) during daytime period, and in 24-hour period (SBP: 127.12 ± 13.65 vs. 121.06± 9.68 mm Hg, p < 0.001 and DBP: 71.87 ± 8.39 vs. 68.75 ± 8.72 mm Hg, p < 0.05) and also increased circulating adiponectin levels (4.04 ± 1.79 vs. 6.00 ± 2.81 ng·ml, p < 0.01). Other genotypes showed no changes in BP and biochemical parameters. Our results suggest a cardio protective factor of I allele because only those homozygous showed reductions in BP and increases in adiponectin.

Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166 C (rs106165) genotypes and psoriasis: Correlation with cellular immunity, lipid profile, and oxidative stress markers.

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A1166 C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A1166 C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A1166 C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A 1166 C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R1166 polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.

Insertion / Deletion Polymorphism of Angiotensin Converting Enzyme Gene Does Not Contribute to Chronic Kidney Disease in Palestine

Background: Chronic Kidney Disease (CKD) is progressive kidney damage in which the glomerular filtration rate (GFR) decreases by 15% of that performed by normal kidneys, with the result that the kidneys are no longer to function effectively and this condition is treated with either kidney transplantation or dialysis. Hemodialysis (HD) is a process in which the blood passes through a machine (dialyzer) to remove waste. Angiotensin Converting Enzyme (ACE) is one of the major components of the renin-angiotensin aldosterone system (RAAS) that is responsible for blood pressure regulation. Insertion/Deletion I/D polymorphism of a 287 bp Alu repeat sequence in introns 16 of the ACE gene results in three genotypes I/D, D/D and I/I. The aims of this study were to evaluate ACE genotypes and allele frequency among HD patients and control subjects and to examine the association between ACE genotypes with HD risk.&#x0D; Methods: A retrospective case-control study included 186 subjects, 86 HD patients and 100 healthy individuals as a control. EDTA whole blood samples were collected from all participants for DNA extraction, and the ACE gene polymorphism was analyzed by using the Polymerase Chain Reaction (PCR) technique. Additionally, all individuals were requested to complete the questionnaire.&#x0D; Results: The initial results demonstrated that the D/D genotype was the most common genotype in all subjects and the association between ACE genotypes with HD occurrence was not statistically significant in the Gaza Strip-Palestine. Furthermore, no statistically significant association was detected between the polymorphism and the study groups (p-value = 0.511).&#x0D;

Association of AGTR1 (A1166C) and ACE (I/D) Polymorphisms with Breast Cancer Risk in North Indian Population

Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3′ untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women. The polymorphisms were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) respectively. The association between these polymorphisms and BCa risk was estimated by calculating Odds Ratio (OR) and chi-square (χ2) test. The DD genotype/D allele of ACE (I/D) polymorphism and “AC and CC” genotype/C allele of AGTR1 (A1166C) polymorphism were associated with higher risk of BCa when evaluated independently. Furthermore, interaction analysis of “AC and CC” and DD genotype and combination of “C and D” alleles of both polymorphisms revealed significantly greater BCa risk than that observed independently. Conclusively, women harboring “AC or CC” genotype/C allele for AGTR1 (A1166C) polymorphism and DD genotype/D allele for ACE (I/D) polymorphisms have a predisposition to develop more aggressive disease with advanced staging and larger tumor size. Our study indicates importance of genetic screening based on these polymorphisms for women, who may have higher risk of BCa.

The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and nicotine dependence in schizophrenia patients.

We investigated the relationship between the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk of nicotine dependence in Croatian schizophrenia patients. We also tested whether interactions between ACE-I/D polymorphism and smoking status affected the clinical psychopathology findings in patients as measured using Positive and Negative Symptom Scale (PANSS) scores. Polymerase chain reaction analysis was used to genotype 267 chronically ill schizophrenia patients (140 males/127 females). There were no significant differences in the distribution of ACE genotypes and alleles in male or female schizophrenia patients who were stratified based on their smoking status. However, there was a trend toward a difference in the ACE genotype distribution in female smokers vs. nonsmokers (χ 2=5.13, p=0.077) that was due mainly to the significant overrepresentation of ACE-ID heterozygous genotypes in female smokers compared to nonsmokers (62.3 vs. 42.0%, p=0.025). ACE-ID heterozygous females had about a twofold higher smoking risk than ACE-II and ACE-DD homozygous carriers (OR=2.29, 95% CI 1.1-4.7, p=0.026). We observed no contribution of the ACE genotype-smoking interaction to PANSS psychopathology. This is the first study to investigate the possible association between ACE-I/D polymorphism and nicotine dependence in schizophrenia. Our results suggest that the ACE-I/D polymorphism may be relevant in determining the risk of nicotine dependence in female patients with schizophrenia while the ACE genotype-smoking interaction does not contribute to the clinical expression of schizophrenia.

The lack of association between angiotensin-converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis.

ObjectiveBlood‐borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin‐converting enzyme (ACE), an enzymatic cascade known as the renin–angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE‐I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE‐I/D polymorphism might influence smoking behavior among patients with MS.Patients and MethodsGenotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.ResultsWe revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE‐I/D polymorphism and either pack‐year smoking history or number of cigarettes smoked daily (p > .05, respectively).ConclusionThe ACE‐I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE‐I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.

Association of the KLK1 rs5516 G allele and the ACE D allele with aortic aneurysm and atherosclerotic stenosis.

Objective:Atherosclerosis underlies aortic aneurysm (AA) and atherosclerotic stenosis (AS). Kallikrein-1 (KLK1) and angiotensin-converting enzyme (ACE) are 2 key molecules in kallikrein-kinin systems and renin-angiotensin systems, respectively, which are responsible for maintaining vascular balance and stability, playing important roles in atherosclerosis. We aimed to assess the involvement of single nucleotide polymorphism rs5516 in KLK1 as well as the insertion/deletion rs4646994 polymorphism in ACE in the development of AA and AS.Methods:We enrolled Chinese Han patients with AA (N = 408) and AS (N = 432), as well as healthy controls (N = 408). Clinical and demographic characteristics were assessed. Genotypes were analyzed with recessive and dominant models.Results:The rs5516 G allele of KLK1 was significantly associated with AA (P < 0.001), and the D allele of ACE was significantly associated with both AA (P < 0.001) and AS (P < 0.001). The GG and DD genotypes were significantly associated with both AA (P = 0.013) and AS (P < 0.001) in a recessive model, and were synergistic with hypertension in AA patients, but not in AS. Patients with CC/DD, CG/ID, or GG/II genotypes, which were synergistic with hypertension, had a greater risk of developing AA, while CC/DD, CG/DD, GG/ID, or GG/DD genotypes, which were not synergistic with hypertension, contributed to the development of AS.Conclusion:The KLK1 rs5516 G allele is closely associated with AA, and the ACE D allele is closely related to AA and AS.

Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study.

BackgroundAccording to the WHO report in 2015, obesity is the fifth leading cause of death worldwide, and the prevalence of Egyptian female obesity is 37.5 %. Since obesity is highly influenced by genetics, and adipose tissue renin-angiotensin system is over-activated in obesity, the effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on obesity and related disorders was studied in several populations, because of its effect on ACE activity. Our objective was to study the association of ACE I/D polymorphism with obesity and certain related disorders, namely hypertension, insulin resistance and metabolic syndrome, in Egyptian females.MethodsEighty female volunteers were recruited, blood pressure and body measurements were recorded and a fasting blood sample was obtained for the quantitation of glucose, lipid profile, insulin, leptin and identification of ACE I/D polymorphs. Subjects were grouped based on hypertension and obesity states. Comparisons of continuous parameters were made with independent sample t-test between two groups. The frequencies of ACE genotypes and alleles, and the association between gene polymorphism and metabolic parameters were assessed using chi-square or Fisher's exact test.ResultsGenotype frequencies were in Hardy-Weinberg equilibrium for all groups. Genotype distribution did not differ significantly between controls and cases of all the studied disorders. Although DD carriers had apparently higher parameters of blood pressure, lipid profile and insulin resistance, only diastolic blood pressure was almost significant (p = 0.057). I-carriers were significantly less susceptible to hypertension than DD carriers having normal waist/hip ratio (p = 0.007, OR = 17.29, CI = 1.81–164.96) and normal conicity index (p = 0.024, OR = 7.00, CI = 1.36–35.93). In DD genotype carriers, a significant association was found between insulin resistance and high body mass index (p = 0.004, OR = 8.89, CI = 1.94–40.71), waist circumference (p = 0.003, OR = 9.63, CI = 2.14–43.36) and waist/height ratio (p = 0.034, OR = 6.86, CI = 1.25–37.61), although the variations in percentages between DD and I-carriers were not high enough to conclude an effect of ACE I/D on such an association.ConclusionsIn this sample of Egyptian females, ACE I/D polymorphism was not significantly associated with obesity nor with any of its related disorders studied. The I allele seemed protective against hypertension in subjects with normal, not high, waist/hip ratio and conicity index compared to DD genotype carriers.

Identification of genetic markers for skill and athleticism in sub-elite Australian football players: a pilot study.

Natural genetic variation contributes towards athletic performance in various strength/power and endurance based sports. To date, no studies have explored the genetic predisposition towards skill and athletic performance in Australian Football (AF) players. The present pilot study recruited 30 sub-elite AF players who completed tests of endurance, power and technical skill. Specific polymorphisms in nine genes were screened, and assessed for a possible association with athletic and skill traits. Statistical analysis using generalized linear models identified a number of polymorphisms predictive of endurance and technical skill. The angiotensin-converting enzyme (ACE), normally responsible for regulation of body fluid volume, was a significant factor in predicting 'all round' athletic performance and skill. Specifically, the deletion allele (DD) of ACE was identified as a predictor for AF power (P≤0.008), endurance (P=0.001) and skill assessments (P≤0.003). In addition, polymorphisms in the brain-derived neurotrophic factor, D2 dopamine receptor, and catechol-O-methyltransferase genes were also shown to contribute to kicking skill outcomes (P≤0.044). This is the first study to implicate the ACE deletion allele for a multidimensional sport in such a way. Further, the results from this study have identified several new candidate genes in predicting athletic and technical skill outcomes.

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and the risk of heart disease: an updated meta-analysis.

Insertion/deletion (I/D) polymorphisms of the gene encoding angiotensin converting enzyme (ACE) are a controversial risk factor for heart diseases (HDs). ACE I/D polymorphism has been reported to be associated with various cardiovascular diseases. However, some studies have presented conflicting results. In this study, we aim to explore the association between ACE I/D polymorphisms and the risk of coronary HD (CHD), coronary artery disease (CAD), and myocardial infarction (MI). A meta-analysis was conducted, which included 12,533 cases and 20,726 controls from 75 case-control studies. We performed overall analysis on the entire dataset and found that the D allele of ACE was significantly associated with increased risk of HDs in three different comparison models (dominant, recessive, and homozygote). We also performed analyses on subgroups based on ethnicity as well as disease type. Our results showed that the D allele of ACE was significantly associated with an increased risk of HDs in the Asian and European groups but not in the American group. In addition, in all three subgroups (CHD, CAD, and MI), the D allele of ACE was found to be significantly associated with increased risk of disease. Begg's funnel plots were generated to evaluate publication biases, but no obvious publication bias was found in the studies included in our meta-analysis. In conclusion, our meta-analysis demonstrated that the D allele of ACE was significantly associated with an increased risk of HDs.

Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients

BackgroundVitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo.ObjectiveOur aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients.MethodsThis case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively.ResultsThe ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P < 0.001) in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007) when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls.ConclusionAs a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.