Polymorphism Of Angiotensin I-converting Enzyme Gene Research Articles

Seeking for associations of I/D polymorphism of ACE gene with self-reported work performance, memory, and cardiovascular health in a professional leadership community

Introduction. Maintaining labor efficiency, working under conditions of stress and uncertainty, high level of requirements to the functional state of workers in various professions actualize the occupational health study of work performance. Methodological applications of predictive medicine and psychogenetics make it possible to identify specific hereditary (biological) predispositions of individuals, to carry out professional orientation of a person, to provide humanistic recommendations on occupation of a certain type of professional activity.
 The study aims to identify a correlation between ACE genotypes and work performance capability in individuals from a professional leadership community.
 Materials and methods. Individuals from a professional leadership community, after dividing into two cohorts consisting of entrepreneurs and non-entrepreneurs, were interviewed and genotyped for evidence of genotype-by-insertion/deletion (I/D) polymorphism associations of the angiotensin I converting enzyme (ACE) gene and health status. Answers to 4 questions characterized the state of work performance and memory, and another 4 questions characterized the cardiovascular system. The mean age was 37±1.7 years for entrepreneurs and 34.23±0.66 years for non-entrepreneurs. There were 44 females and 129 males among them.
 Results. Analysis of genotyping of 173 people (25 entrepreneurs and 148 non-entrepreneurs) revealed a significant deviation of actual frequencies of I and D alleles from theoretically expected values in the whole group of managers and between non-entrepreneurs (p=0.95, χ2>3.8). In all groups, there was a marked increase in the frequency of the I/I genotype at the expense of a decrease in the frequency of the D/D genotype compared to the literature data. A significant difference between D/D and I/D genotypes in work performance was found in entrepreneurs (p=0.9817), which coincides with a significant difference between their representatives by age (p>0.99). Contrary to expectations, representatives of the D/D genotype, at least entrepreneurs, demonstrated the most optimal level of functioning of the autonomic nervous system. No associations were found between the genotype for the ACE gene (rs4646994) and work performance and memory.
 Conclusion. In the total sample of leaders and among the subgroup of non-entrepreneurs, a strong and reliable change in the frequencies of alleles I and D was found compared to the theoretically expected (frequencies). There was a significant increase in the frequency of I/I genotype in all groups. The significant difference in the rates between the D/D and I/D groups coincides with a significant difference between their representatives in terms of age. According to the results of test answers, representatives of entrepreneurs of D/D genotype had the most optimal level of vegetative nervous system functioning.

GENETIC ASPECTS OF PROOXIDANT-ANTIOXIDANT BALANCE IN PATIENTS WITH DIABETIC NEPHROPATHY

The aim of this work is to study the state of the prooxidative-antioxidant balance in patients with diabetic nephropathy depending on the functional state of the kidneys and taking into account the polymorphism of ACE gene. Participants and methods. This study involved 82 patients with type 2 diabetic and nephropathy. The control group consisted of 20 healthy individuals. The prooxidant-antioxidant balance of blood serum was calculated as the ratio of total hydroperoxide content to total antioxidant activity. The content of total hydroperoxides and total antioxidant activity were determined by the colorimetric method. Results. Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. Angiotensin I-converting enzyme (ACE) gene polymorphism is associated with the development and progression of acute and chronic kidney diseases. However, the features of antioxidant protection in patients with diabetic nephropathy, who are carriers of different genotypes of this polymorphism, have not been studied. Association analysis using the SNPStats online program has demonstrated that in patients with diabetic nephropathy, the I/I polymorphism is associated with an increase in the concentration of total hydroperoxides in blood serum (difference = 23.62 (6.16-41.08); p = 0.017 — codominant model inheritance; difference = 22.73 (7.70-37.75); p = 0.0042 — recessive model of inheritance). We found a significant increase of total hydroperoxides in diabetic nephropathy patients - carriers of the homozygous I/I genotype of the ACE gene polymorphism, compared to carriers of the D-allele (I/D and D/D genotypes), p=0.03.The highest values of prooxidant-antioxidant balance of blood serum in patients with diabetic nephropathy are noted in carriers of the I/I and I/D genotypes of the ACE gene/ These findings may indicate a negative effect of the I allele on the general state of the prooxidant-antioxidant balance in this category of patients. Conclusions. The analysis of the data we obtained allows us to assume an important influence of the ACE gene polymorphism on the pathogenesis of diabetic kidney disease due to changes in the prooxidant-antioxidant balance in patients with type 2 diabetes.

No Association of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) Gene Polymorphism in the Susceptibility to Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients: An Updated Meta-Analysis.

Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in the development and progression of DR, the Angiotensin I-converting enzyme (ACE) gene stands out, which presents an insertion (I) or deletion (D) polymorphism of a 287 bp Alu repetitive sequence in intron 16. Thus, this study aimed to perform a systematic review with meta-analysis to elucidate the relationship between the ACE gene (I/D) polymorphism (rs1799752) and the development and progression of DR in type 2 diabetic patients. PubMed/MEDLINE, Embase, Web of Science, and Scopus databases were systematically searched to retrieve articles that investigated the association between ACE gene (I/D) polymorphism in DR patients. Sixteen articles were included in the systematic review. The results describe no significant association between the polymorphism and DR risk (OR = 1.12; CI = 0.96-1.31; and p = 0.1359) for genotypic analysis by the dominant model (II vs. ID+DD). Moreover, we also observed no significant association between the D allele on the allele frequency analysis (I vs. D) and the DR risk (OR = 1.10; CI = 0.98-1.23; and p = 0.1182). Forest plot analysis revealed that the discrepancy between previous studies most likely arose from variations in their sample sizes. In conclusion, I/D polymorphism appears to be not involved in the susceptibility to and progression of the DR in type 2 diabetic patients.

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

BackgroundAdiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood.MethodsThis study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan.ResultsResults showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG.ConclusionsIn this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Association of the angiotensin I converting enzyme (ACE) gene polymorphisms with recurrent aphthous stomatitis in the Czech population: case\u2013control study

BackgroundRecurrent aphthous stomatitis (RAS) is multifactorial disease with unclear etiopathogenesis. The aim of this study was to determine distribution of the angiotensin I converting enzyme (ACE) gene polymorphisms and their influence on RAS susceptibility in Czech population.MethodsThe study included 230 subjects (143 healthy controls and 87 patients with RAS) with anamnestic, clinical and laboratory data. Five ACE gene polymorphisms (rs4291/rs4305/rs4311/rs4331/rs1799752 = ACE I/D) were determined by TaqMan technique.ResultsThe allele and genotype distributions of the studied ACE I/D polymorphisms were not significantly different between subjects with/without RAS (Pcorr > 0.05). However, carriers of II genotype were less frequent in the RAS group (OR = 0.48, 95% CI = 0.21–1.12, P = 0.059). Stratified analysis by sex demonstrated lower frequency of II genotype in women (OR = 0.33, 95% CI = 0.09–1.17, P < 0.035, Pcorr > 0.05, respectively) than in men with RAS (P > 0.05). Moreover, the frequency of AGTGD haplotype was significantly increased in RAS patients (OR = 13.74, 95% CI = 1.70–110.79, P = 0.0012, Pcorr < 0.05). In subanalysis, TGD haplotype was significantly more frequent in RAS patients (P < 0.00001) and CGI haplotype was less frequent in RAS patients (P < 0.01), especially in women (P = 0.016, Pcorr > 0.05).ConclusionsOur study indicates that while the AGTGD and TGD haplotypes are associated with increased risk of RAS development, CGI haplotype might be one of protective factors against RAS susceptibility in Czech population.

Is Angiotensin Converting Enzyme Insertion/Deletion (rs1799752) Polymorphism Associated with Breast Cancer Risk in Egyptian Population?

Background: According to GLOBOCAN estimates, breast cancer was found to be the most often diagnosed cancer in women worldwide, (11.7 %) and the fourth leading cause of cancer mortality (6.9 %).&#x0D; Aim: The purpose of this study is to investigate the role of the Angiotensin I-converting enzyme (ACE) gene polymorphism in breast cancer prediction risk in Egyptian population.&#x0D; Methods: Polymorphism detection analysis was performed on 163 subjects from breast cancer (BC) patients, 79 with Benign Breast Disease group (BBD) patients and 202 controls (C). ACE I/D (rs1799752) polymorphism were detected using polymerase chain reaction (PCR).&#x0D; Results: The observed genotype frequencies were II 10.9%, ID 78.2% and DD 10.9% in healthy control, II 8.6%, ID 79.1% and DD 12.3% in BC patients and II 12.6%, ID 78.4% and DD 9% in BBD patients. There were no association between ACE gene polymorphisms, between the BC or BBD groups when compared to the control group (ORDD= 1.43, 95 % CI= (0.58-3.52), P= 0.29) and (ORDD= 1.29, 95 % CI= (0.57-2.95), P= 0.37) respectively. There was no risk estimate in BC or BBD when DD vs II + ID (Recessive) or ID vs II+ DD (Over-dominant) were compared to control. Allele frequencies show the same figure. From the different histological BC hormonal markers the Her2 was showing significant association in ID genotype of ACE I/D (rs1799752) (P= 0.04) and dominant model (II vs ID + DD, P= 0.03). Concerning different BC prognostic models, the poor prognostic one of Her2 enriched model (ER-ve PR-ve Her2+ve) show significant association in ACE genotype ID and dominant model (II vs ID + DD), (P= 0.01) when compared to the good prognostic hormonal status.&#x0D; Conclusion: It seems that this is the first study that interested in correlate the ACE gene polymorphisms in different BC variants characters in Egyptian patients. ACE I/D (rs1799752) polymorphism ID genotype have strong association to breast cancer carcinogenesis, poor prognosis and metastasis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.

ACE Insertion/Deletion gene polymorphism and genomic sequence in Diabetic nephropathy

Insertion/deletion polymorphism of the angiotensin I converting enzyme (ACE) genetically determines most of the plasma ACE activity. Modulation of ACE gene activity might have an important bearing on the rate of progression of renal disease, though its exact role in the nephropathy of type 2 diabetes (T2DM) is far from clear. This prospective, cross-sectional, observational study was designed to study the correlation between insertion/deletion polymorphism of ACE gene in diabetic nephropathy. T2DM cases (n=30) were evaluated, regarding duration, onset and degree of albuminuria, renal insufficiency and hypertension. All patients underwent detailed clinical and biochemical evaluation. Genomic DNA intron 16 of the ACE gene was amplified by polymerase chain reaction (PCR) followed by sequencing. The mean age of this study group was 45.21±2.34 yrs. PCR amplification of ACE gene fragments revealed insertion/insertion (I/I, n =8); insertion/deletion (I/D, n = 18) and deletion/deletion (D/D, n = 4) alleles. All three groups were matched age-wise. Micro- and macro-vascular complications were more prevalent in DD type (p=0.012). The majority (75%) of patients with II allele took a longer time to develop overt albumiuria, having lesser hypertension, renal dysfunction, and dyslipidemia than ID and DD allele (p<0.005). On the other hand, urinary albumin excretion, systemic and diastolic blood pressures, triglycerides, serum creatinine and low density lipoprotein-C were significantly higher (p<0.005), in patients of DD type than II and ID groups. This finding suggests that patients with DD allele of the ACE gene are more likely to have progressive diabetic nephropathy with micro- and macro-vascular complications.

ACE gene rs4343 polymorphism elevates the risk of preeclampsia in pregnant women.

The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk factors that are important in the development of the disease. Therefore, the exact etiology and pathogenesis of preeclampsia remains unclear. It is suggested that inappropriate regulation of the renin-angiotensin system (RAS) is a risk factor for hypertension during pregnancy. The angiotensin I-converting enzyme (ACE) serum level, a key component of the RAS, affects the blood pressure. It is hypothesized that the ACE gene polymorphisms contribute to preeclampsia development. In a case-control study containing 296 subjects (165 PE patients and 131 normotensive controls), we aimed to examine the association of the ACE gene I/D and rs4343 polymorphisms with preeclampsia in Iranian women. Genotyping for rs4343 and ACE I/D polymorphisms was performed by using TP-ARMS-PCR and conventional PCR, respectively. The rs4343 G allele frequency was higher in the case group (OR = 1.90, 95% CI, 1.37-2.65; P = 0.0001). Besides, a significant difference was detected for the genotype frequencies between the studied groups under dominant (OR = 3.94, 95% CI, 2.05-7.56; P < 0.0001) and recessive (OR = 2.21, 95% CI, 1.22-4.01; P = 0.009) inheritance models. For the I/D polymorphism, no significant differences were detected in the genotype and allele frequencies or any of the inheritance models between PE patients and controls. To verify the current results and validate the significance of the studied genetic variations, additional studies in diverse ethnic populations are required.

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population.

BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients.OBJECTIVETo investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients.DESIGNCase-control study.SETTINGTertiary care center, Riyadh.METHODSTwo hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis.MAIN OUTCOME MEASUREThe strength of association between the Q192R polymorphism and FH in the Saudi population.RESULTSWe confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05–3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13–3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09–2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population.CONCLUSIONIn conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH.LIMITATIONOnly a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population: the hisayama study.

The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval=2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID＋II genotype; P for interaction=0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample

The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population.

Angiotensin I converting enzyme (ACE) insertion and deletion (I/D) polymorphism has been implicated in the pathogenesis of osteoarthritis (OA). In recent years, numerous genetic factors have been identified and implicated in OA. In this Asian Indian population-based study, we aimed to evaluate the relationship between ACE (I28005D) gene polymorphism and primary OA. We performed a case-control association study to identify and explore the correlation between clinically, radiologically diagnosed individuals with primary knee OA and the ACE I/D polymorphism. Genomic DNA was isolated from 200 samples, including 100 OA cases and 100 healthy volunteers. DNA was amplified by polymerase chain reaction (PCR) using I and D allele-specific primers. PCR products were assessed via UV visualization of products electrophoresed on 2% agarose gels. The groups differed significantly in genotype distributions (p < 0.05). The primary knee OA group showed a considerably higher incidence of the DD genotype and the D allele compared to the control group (OR = 2.14, 95% CI: 1.10-4.15, p = 0.02 and OR = 2.08, 95% CI: 1.39-3.10, p = 0.0003). The ACE gene polymorphism I28005D was found to be associated with primary knee OA in Asian Indian populations. This is the first study in India to report that the ACE gene polymorphism is a risk factor for early onset primary knee OA.

Association of insertion–deletion polymorphism of ACE gene and Alzheimer’s disease in Egyptian patients

IntroductionAlzheimer’s disease (AD) is a progressive, neurodegenerative disease. Many studies proposed an association of the insertion (I)/deletion (D) polymorphism (indel) in intron 16 of the gene for angiotensin I-converting enzyme (ACE) on chromosome 17q23 with Alzheimer’s disease. ACE indel and related haplotypes associated with AD risk have reduced plasma ACE whereas protective genotypes have elevated ACE. ObjectTo investigate whether there is a correlation between polymorphisms of the ACE I/D locus gene and AD in Egyptian patients and to determine whether there is a difference in ACE activity in the plasma of clinically diagnosed AD patients. MethodsSubjects of this study are 84 dementia patients diagnosed as having Alzheimer’s disease, 45 males and 39 females aged 65±7years from the Geriatric Department at Ain-Shams University Hospitals and 86 individuals as non dementia controls, 44 males and 42 females aged 63±6years.All subjects were genotyped for the common insertion/deletion polymorphisms for ACE gene locus, and ACE plasma activity assay was measured for AD patients. ResultsThere was statistically significant difference in the frequency of the ACE insertion/deletion alleles between the cases and controls where the I allele distribution in AD cases and controls was 74% vs. 15%, and the I/I genotype frequency was 60% vs. 5%, respectively. They both reached a statistical significance range (I allele frequency: OR=3.714, 95% CI 1.311–10.523, p<0.01; I/I genotype frequency: OR=3.18 95% CI 2.33–4.33, p<0.01). But no significant difference in ACE plasma level was found between different genotypes in our AD patients. ConclusionsOur present study supports the hypothesis of implication (I allele) of ACE gene polymorphism in the development of AD. On the other hand, we did not find significant difference in plasma ACE activities when compared with different studied genotypes.

Endometriosis and RAS System Gene Polymorphisms: The Association of ACE A2350G Polymorphism with Endometriosis in Polish Individuals

To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

The use of Angiotensin-I converting enzyme i/d genetic polymorphism as a biomarker of athletic performance in humans.

Angiotensin II is a key regulator of blood pressure and cardiovascular function in mammals. The conversion of angiotensin into its active form is carried out by Angiotensin I-Converting Enzyme (ACE). The measurement of ACE concentration in plasma or serum, its enzymatic activity, and the correlation between an insertion/deletion (I/D) genetic polymorphism of the ACE gene have been investigated as possible indicators of superior athletic performance in humans. In this context, other indicators of superior adaptation to exercise resulting in better athletic performance (such as ventricular hypertrophy, VO2 max, and competition results) were mostly used to study the association between ACE I/D polymorphism and improved performance. Despite the fact that the existing literature presents little consensus, there is sufficient scientific evidence to warrant further investigation on the usage of ACE activity and the I/D ACE gene polymorphism as biomarkers of superior athletic performance in humans of specific ethnicities or in athletes involved in certain sports. In this sense, a biomarker would be a substance or genetic component that could be measured to provide a degree of certainty, or an indication, of the presence of a certain trait or characteristic that would be beneficial to the athlete’s performance. Difficulties in interpreting and comparing the results of scientific research on the topic arise from dissimilar protocols and variation in study design. This review aims to investigate the current literature on the use of ACE I/D polymorphism as a biomarker of performance in humans through the comparison of scientific publications.

Polymorphism of angiotensin I-converting enzyme gene is related to oral cancer and lymph node metastasis in male betel quid chewers

Angiotensin I-converting enzyme (ACE), a type I cell surface zinc metallopeptidase, is differentially expressed in several malignancies and plays a role in tumor cell proliferation, tumor cell migration, angiogenesis, and metastatic behavior. We aimed to investigate the effects of ACE gene (rs1799752) variants on oral cancer risk. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) 32 was used to measure ACE gene polymorphisms in 88 patients with oral precancerous lesion (OPL), 186 33 patients with oral cancer, and 120 control subjects without any oral lesions. All study subjects were male 34 betel quid chewers. Patients with oral cancer or OPL had a higher frequency of the DD genotype than the control patients did. Oral cancer patients with the DD genotype had a significantly higher prevalence of lymph node metastases than patients with the II/ID genotype did. After adjusting for age, smoking, drinking, and betel quid chewing status, we found that individuals with the DD genotype of the ACE gene had a 5.46-fold and 3.13-fold higher risk of developing oral cancer or OPL, respectively, than those with the II genotype did. Furthermore, oral cancer patients with the DD genotype of the ACE gene had a 2.16-fold higher likelihood of lymph node metastasis. Our data suggest that the ACE gene polymorphisms may be associated with increased susceptibility to OPL and oral cancer and lymph node metastasis from oral cancer.

Gene Polymorphism in Angiotensin-I-Converting Enzyme and Physical Activity Among Normotensive Chinese

The angiotensin-I-converting enzyme (ACE) I/D gene polymorphism has been studied for its role in determining habitual physical activity level, but there is no information from Asian populations. The objective of this study was to determine whether this ACE gene polymorphism was associated with physical activity level among Chinese in Singapore. In this cross-sectional study, 110 normotensive Chinese in Singapore, age 21-61 yr, completed the short-form version of the International Physical Activity Questionnaire and contributed buccal cell samples for genotyping of the ACE I/D gene polymorphism using polymerase chain-reaction amplification. They also provided demographic information and underwent anthropometric measurements. Physical activity level was expressed as continuous (in kcal/wk) and categorical (low, moderate, or high) data. The 3 genotypes of ACE were DD (homozygous for the deletion allele), II (homozygous for the insertion allele), and ID. Among the participants, 28.2% reported low, 49.1% moderate, and 22.7% high physical activity level. Frequencies of the genotypes were 11.8% for DD, 42.7% for ID, and 45.5% for II. ACE genotype was independently associated with physical activity level. After age, gender, and body-mass index were adjusted for, individuals with DD or ID genotypes were more likely to report insufficient or low physical activity level than those with II genotypes (odds ratio = 6.88; 95% confidence interval: 2.26, 20.94). In conclusion, the I/D polymorphism of the ACE gene is significantly associated with self-reported physical activity level in normotensive Chinese Singaporeans.

Angiotensin I-Converting Enzyme Gene Polymorphism and Diabetic Nephropathy in Filipino Type 2 Diabetes Mellitus Patients

Objective. Previous studies have demonstrated the role of genetic susceptibility in the pathogenesis of diabetic nephropathy. The study aimed to determine the frequencies of angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in a pilot population of Filipino type 2 diabetic patients and normal controls. Methods. An analysis of the ACE gene polymorphism was performed in 42 diabetic patients with and without nephropathy, and 24 normal controls. The analysis was done using polymerase chain reaction, restriction enzyme digestion, and gel electrophoresis techniques to determine the polymorphism (II, DD or ID). Independent T-tests and chi-square tests were used to compare clinical characteristics, and logistic regression analysis was done to determine odds ratio for development of nephropathy. Results. The ID polymorphism of the ACE gene was more frequent (52.4%) in patients with diabetic nephropathy (n=21). In those without nephropathy (n=21), II was more common (61.9%). ID was the more frequent genotype in the normal controls (n=24) (58.3%). The odds of developing diabetic nephropathy were increased by 4.8 times in those with ID polymorphism, and 2.9 times in those with DD. Conclusion. The D allele was more common in patients with diabetic nephropathy, similar to the observation in South Indian patients. Since the study involved only a small pilot group, studies on a larger population is needed to establish the hypothesized role of the D allele in susceptibility to diabetic nephropathy in Filipinos.

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The angiotensin I converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension and IR. The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS. In a case-control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into three groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology; Group B, clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology; and Group C, chronic anovulation and polycystic ovarian morphology. A significant increase in the frequency of the DI genotype of the ACE polymorphism was detected in PCOS women as a whole (P=0.035), in PCOS Group A (P=0.039) and Group B (P=0.010), while there was no difference in Group C (P=0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group A+B) (P=0.017). The II genotype was positively correlated with HOMA-IR and QUICKI and with fasting insulin and glucose/insulin ratio in these groups. The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence and an association of the II genotype with IR.

ACE gene polymorphism and serum ACE activity in Iranians type II diabetic patients with macroalbuminuria

There are controversial results related to the contribution of insertion (I)/deletion (D) polymorphism of the angiotensin I-converting enzyme (ACE) in the development of diabetic nephropathy. To assess the distribution of this polymorphism in diabetic patients with and without nephropathy we studied 140 unrelated type 2 diabetic patients from the Kermanshah Province of Iran with ethnic background of Kurds including 68 patients with macroalbuminuria and 72 normoalbuinuric diabetic patients as controls. Genotyping was done by polymerase chain reaction (PCR). The frequency of D allele in nephropathic and normoalbuminuric patients were 69.1 and 58.3%, respectively (P=0.061). In individuals with DD genotype the risk of macroalbuminuria increased 2.87-fold (P=0.057). Significant lower level of serum ACE activity was found in the normoalbuminuric (59.76IU/l) compared to macroalbuminuric (97.43IU/l) patients. The serum ACE activity was significantly higher in macroalbuminuric patients with ID (105.7IU/l) and ID+DD (100.7IU/l) genotypes compared to normoalbuminuric patients with the same genotypes (63.5 and 64.2IU/l, respectively). Treatment with captopril significantly (P=0.045) reduced the serum ACE activity in normoalbuminuric patients with DD genotype compared to macroalbuminuric patients with the same genotype (33.6 vs. 73.8IU/l). However, the greatest benefit effect of losartan therapy on ACE activity was observed only in macroalbuminuric patients with DD genotype compared to that in normoalbuminuric patients (61.0 vs. 109.0IU/l, P=0.06). Our study suggests the importance of ethnic origin in the development of diabetic nephropathy and demonstrates different responses to therapy according to genotype and stage of diabetes.