ACE gene, physical activity, and physical fitness.

The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case-control study of the ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirate nationals, composed of two groups: 112 subjects above 18 years of age (range=20-77 years), and 52 subjects of 18 years or less (range=1-18), and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individuals were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects by colorimetric assays. The D allele was associated with increased ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42%-61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. The ACE*I/D dimorphism correlated strongly with circulating ACE activities in both adult and young Emirati subjects, and the corresponding mean ACE activities were significantly higher among the youngsters.

Angiotensin-converting enzyme (ACE) gene has been associated with the pathogenesis and progressi on of chronic kidney diseases. Diabetic nephropathy has b ecome leading cause of renal end stage disease (ESRD). An I/D polymorphism of angiotensin-converting enzyme (ACE) gene has been suggested as one of the risk factors for the progression of diabetic nephropathy. We analyzed th e genotype and allele frequency distribution of ACE g ene in 166 Type 2 diabetic patients without any complicati on (T2DM), 61 with diabetic nephropathy (DN), 50 with non- diabetic nephropathy (NDN) and 50 healthy individ uals from western Indian population. ACE genotype was analyzed by PCR method. The D allele distributio n for the ACE I/D polymorphisms was not significantly different between control group and patients with T2DM without any complication (41.0% vs. 45.2%, P= 0.461) and between control subjects and patients with non-diabetic nep hropathy (NDN) (41.0% vs. 44.0%, P= 0.668). Frequency of the D allele (63.9% vs. 45.2%, P < 0.001) and DD genotype (I allele noncarrier) (44.3% vs. 25.3%, P= 0.006) of ACE gene was significantly higher in patients with diab etic nephropathy (DN) than in patients with T2DM without any complication. Results of the present study in dicate that ACE gene polymorphism does not have significant influ- ence on development of diabetes mellitus and nondia betic nephropathy, whereas, the DD polymorphism in ACE gene has been associated with the development of diabeti c nephropathy in the Western Indian population.

Purpose : Human angiotensin converting enzyme (ACE) gene shows an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by whether a 287 bp fragment of the DNA is present or not; II, ID and DD genotype. DD genotype has been suggested as a risk factor of chronic nephrotic disease such as IgA nephropathy and diabetic nephropathy, various cardiovascular diseases and several other diseases. ACE activity increases in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis and cirrhosis. On the other hand, patients with fatty livers have normal ACE activity. This study was designed to find out the relation between polymorphsims of the ACE genes and neonatal hyperbilirubinemia in Koreans. Methods : The genomic DNA was isolated from 110 full-term Korean neonates who had hyperbilirubinemia with no obvious causes (serum bilirubin 12 mg/dL) and 164 neonates of a control population (serum bilirubin12 mg/dL). We performed polymerase chain reaction (PCR) to see the allele of the ACE gene. Electrophoresis was done in the PCR products in 1.5 percent agarose gel, and then DNA patterns were directly visualized under ethidium bromide staining. Results : ACE genotypes in the hyperbilirubinemia group are as follows; 26.36 percent for II, 53.64 percent for ID, 20.00 percent for DD, 0.532 for I allele and 0.468 for D allele. These distributions were not significantly different from those in the control group; 24.39 percent for II, 51.83 percent for DI, 23.78 percent for DD, 0.503 for I allele and 0.497 for D allele. Conclusion : In this study, ACE gene polymorphism was detected in the neonatal hyperbilirubinemia and control group. The most frequent genotype was ID. Our results indicate that the ACE gene polymorphism is not associated with the prevalence of neonatal hyperbilirubinemia in Koreans.

To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis. In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17). The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. Sixty-two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19-75 years, median age/range at study 47.5/22-81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40-82 years) served as controls. S-ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S-ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy-Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over-represented in X-ray stage III compared to the other X-ray stages (P = 0.0181) and a significant increase in the DD genotype in X-ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected. We confirmed that the S-ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S-ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X-ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S-ACE it encodes.

Genetic factors are important in the pathogenesis of coronary artery disease (CAD). The I/D polymorphism in the Angiotensin converting enzyme (ACE) gene is a genetic risk factor for CAD patients who have a history of Myocardial Infraction (MI). We investigated the association between I/D polymorphism of the ACE gene and the presence of CAD in one hundred patients (79 males and 21 females, aged between 21- 82) who underwent diagnostic coronary angiography and compared with one hundred patients-as controls (62 males and 38 females, aged between 20- 72) who had false symptoms of CAD. The presence of risk factors including age, hypertension, hypercholesterolemia, tobacco use, diabetes mellitus and hyperuricemia was also determined. ACE I/D polymorphism was detected by polymerase chain reaction. The D allele frequency was higher (p <0-01) in CAD patients. The logistic regression analysis indicated that the D allele in association with classical risk factors had the potential to induce CAD, with odds ratio = 0.58(95% CI; 0.37-0.90). This study revealed that, the I/D polymorphism of ACE gene (carrying D allele) was found to be an independent risk factor for CAD in the studied South Indian population. The number of risk factors did not alter the frequency of ACE gene genotype among patients with CAD, however, in normotensives, the odds ratio of DD-genotype was significantly higher, as the D allele of ACE gene polymorphism was found to be associated with morbidity in CAD in this study population. Key words: ACE gene polymorphism, coronary artery disease, myocardial infarction, risk factors.

To explore the distribution of I/D polymorphisms of angiotensin converting enzyme (ACE) gene and its relation to natural longevity in the Xinjiang Uygur people. Polymerize chain reaction, single strand conformation polymorphism, and direct sequencing technique were used to test the I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, 53 cases of natural death aged 65-70 were used as controls. The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and 40.5% respectively in the centenarian group, the frequency rates of D and I alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian group was significantly higher than that of the group aged 65-70 (28.6% vs. 12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of the group aged 90 (P > 0.05). The frequency rate of D allele of the group of centenarian was significantly higher than that of the group aged 65-70 (44.0% vs. 36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls (both P < 0.01). ACE gene polymorphism is closely correlated with life span of individuals. Longevity is the result of pleiotropic age-dependent influence of multiple factors.

The ACE gene has received substantial attention in recent years as candidate for a variety of diseases. The most common polymorphism in ACE gene is the Insertion/Deletion (I/D, rs4646994) polymorphism located on intron 16. We investigated the association between metabolic syndrome (MS) and the insertion (I) - deletion (D) polymorphisms in the angiotensin converting enzyme (ACE) gene in south-east of Turkey. One hundred and sixty subjects, with 101 cases of MS and 59 age- and gender-matched healthy controls were included in the study. The frequency of ACE I/D polymorphism was found to be 49.5% for DD, 36.6% for ID, and 13.9% for II in the MSstudy group and 44.1% for DD, 42.4% for ID and 13.5% for II in the control group. Allele frequencies were found to be 0.68% for D and 0.32% for I allele in the study group with MS and 0.65% for D, 0.35% for I allele in the control group. The I/D polymorphism of the ACE gene, DD, ID, and II genotypes occurred with similar frequencies in the study group with MS and the control group with no significant differences (p<0.05). On applying one-way analysis of variance to different ACE gene polymorphic groups in patients with MS were not significantly associated to ACE gene polymorphism and waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HDL, and LDL (p<0.05). Further studies of patients in larger numbers and of different ethnic backgrounds may be necessary to elucidate the association between the ACE I/D gene polymorphism and MS.

Background:Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI).Objective and Methods:The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated.Results:The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively).Conclusion:Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

To investigate the potential association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE activity with pregnancy-induced hypertension (PIH). The ACE genotype was identified and serum ACE activity was measured in 50 primigravidae with PIH and 50 normotensive primigravidae. These subjects were followed up to delivery and perinatal outcome noted. ACE DD genotype was found in 60% of subjects with PIH but only in 30% of normotensive subjects (P = 0.004). The odds ratio for developing hypertension in subjects with DD genotype was 3.5. The incidence of D allele of ACE gene was significantly higher in hypertensive subjects (0.74) than in normotensive subjects (0.56, P = 0.011). The odds ratio for developing hypertension in subjects with D allele was 2.24. However, the ACE genotype was similar in different categories of PIH and did not affect the perinatal outcome. The mean ACE activity in the hypertensive subjects (32.4 IU/l) and the normotensive subjects (23.7 IU/l) was similar (P = 0.092). The ACE activity did not differ significantly according to ACE genotype. We noticed an excess of DD genotype and D allele in ACE gene in PIH. However, this polymorphism does not correlate with the severity of hypertension or perinatal outcome. Serum ACE levels do not correlate with the ACE gene polymorphism or the development of PIH.

ABSTRACTIntroductionIn this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease.Materials and methodsLiver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification.ResultsA total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= −0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92).ConclusionIn this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD.How to cite this articleTekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin–Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

Abstracts of Literature

To assess the potential association between the angiotensin converting enzyme (ACE) gene polymorphism and the activity of the renin-angiotensin system in a Japanese population, we determined the ACE genotype and its enzyme activity in serum in 108 young Japanese females. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers flanked the polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID and II ACE genotypes was 10, 55 and 35%, respectively. The estimated allele frequencies of the deletion and the insertion were 0.375 and 0.625, respectively. The mean serum ACE activity in DD subjects was about 1.4 times that of II subjects (p < 0.01), with ID subjects having intermediate levels (p < 0.05), whereas the renin profile were not statistically different among the three groups. These results indicate a significant association between ACE gene polymorphism and serum ACE activity levels, suggesting a mechanism by which genotype might have a hearing on the physiology of the renin-angiotensin system axis.

Objective To explore the relationships between angiotensin converting enzyme (ACE) gene polymorphism of insertion/deletion(I/D) and cognition function in senile depressive patients in Chinese Han population. Methods 97 patients with major depression were recruited according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, and 103 healthy persons were used as controls. The Hamilton Depression Scale (HAMD) and neuropsychological tests were used to assess depressive severity and cognitive function in all patients and 44 healthy controls, respectively. The intron 16 I/D polymorphism of ACE gene was detected by polymerase chain reaction (PCR). Results The performances of neuropsychological tests in case group except TMT B were significantly poorer than those in control group (P 0.05). Furthermore, no significant differences of neuropsychological test performances were found between ACE genotypes of senile depressive patients(P>0.05). Conclusion Senile depressive patients have extensive cognitive impairments in the acute phase of illness, and working memory performance is correlated with depression severity. ACE gene I/D polymorphism may not significantly associate with cognitive function in senile patients. Key words: Senile depressive patients; Cognitive function; Angiotensin converting enzyme; Gene

SUN-218 Evaluation of common polymorphisms of eNOS gene and ACE gene in ADPKD patients and their association with HTN and renal failure in ADPKD patients

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n=43) was lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects homozygous for the D allele (44.0+/-7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n=25) than among controls (29.4 U/l, n=43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.