Angiotensin I-converting Enzyme Polymorphism Research Articles

The Relationship of Angiotensin I-Converting Enzyme Genotype to Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

AbstractBackground: Multiple genetic and environmental factors may lead to fibrogenesis in patients with Non-alcoholic fatty liver (NAFL). Many studies investigated the relation of angiotensin I-converting enzyme (ACE) genotyping to liver fibrosis in chronic liver disease; and the results are contradic-tory.Aim of Study: In the current study, ACE genotype was assessed in NAFLD patients to show its possible association with development liver fibrosis.Subjects and Methods: The study included 162 patients of NAFLD disease, 49 (30.25%) patients with mild fibrosis, 65 (40.12%) with moderate fibrosis and 48 (29.63%) with severe fibrosis in addition to 138 volunteers was enrolled as a healthy controls. All patients and controls were investigated to serum glucose and fasting insulin level and HOMA-IR was calculated. Liver function tests, both serum ACE and trans-forming growth factor-beta (TGF-b) were done. ACE geno-typing [insertion/deletion (I/D)] was done by PCR.Results: Fasting glucose and insulin, HOMA-IR, AST, ALT and GGT were significantly higher in NAFLD patients than healthy controls. The homozygous frequency I/I and D/D or D/I of ACE were not significantly different between NAFLD patients and controls. The D/D genotype was associated significantly with the severity of liver fibrosis, D/I polymor-phism with moderate fibrosis and I/I genotype with mild fibrosis. The higher D allele frequency was associated with severe fibrosis, while I allele was frequent in mild fibrosis. The HOMA-IR, ALT, serum ACE and TGF-b were increased significantly in the patients carrying D/D homozygous gene more than those carrying homozygous I/I or D/I polymorphism. The serum ACE and TGF-b were significantly higher in NAFLD patients compared to control and the most higher levels was reported in cases with severe liver fibrosis than moderate and mild liver fibrosis.Conclusion: ACE (D/D) genotype was closely associated with liver fibrosis severity and ACE (I/D) polymorphism was observed in moderate stage of fibrosis. The allele D is seems to be a risk factor for liver fibrosis development than allele I. The knowledge of the ACE genotypes in NAFLD patients may be important for treatment decision in those patients and beneficial in the follow-up of the disease progression.

PO-008 Influences of ACE I/D and ACTN3 R577X polymorphisms in elite female soccer athletes

Objective The performance phenotype is regulated by polygenes .There were few reports about the cumulative effect of the I/D polymorphism in the angiotensin I-converting enzyme (ACE) gene and ACTN3 in athletes.This study was to investigate the association of ACEI/D and ACTN3 R577X polymorphisms with the performance of Chinese elite female soccer athletes for the first time. 
 Methods The genotype distributions of ACE I/D and ACTN3 R577X in the athlete group (N=92) and the control group of Chinese females (N=200) were evaluated via PCR and compared.
 Results Regarding the distribution of ACE polymorphisms, the genotype frequency was indifferent between the athletes (II 40.2%, ID 46.7%, DD 13.1%) and the controls (II 42%, ID 48%, DD 10%) based on the chi-square test. No difference in the I/D allele frequency was observed between the athlete group (I allele: 59.25%; D allele: 40.75%) and the control group (I allele: 60.8%; D allele: 39.2%). Regarding the distribution of ACTN3 polymorphisms, the genotype frequency was significantly different between the athletes (XX 0%, XR 53.3%, RR 46.7%) and the controls (XX 16%, XR 44%, RR 40%). The allele frequency was observed no different between the athlete and the control group (X allele:34.8%/41.7%; R allele: 65.2%/58.3%, respectively). The ACE and ACTN3 genotype combinations (II/ID/DD+RR/XR) significantly differed between the athletes and the controls by χ2 test (p<0.05).
 Conclusions These results suggested that the Chinese elite female soccer athletes were more likely to harbor the I allele and the R allele and that the combination of ACE II/ID and ACTN3 RR/XR was a synergetic determinant of the athletic performance of females in soccer.

Association between Thrombophilic Gene Polymor-phisms and Recurrent Pregnancy Loss in Iranian Women

Background: Recurrent pregnancy loss (RPL) is a common problem among couples, and acquired thrombophilia is the well-known etiology of RPL. The aim of this study was to establish the association between inherited thrombophilic gene polymorphisms and RPL. Methods: This case-control study was conducted on 50 women with unexplained RPL and 50 parous women with no history of miscarriage (age range: 17–48 years). The data were collected during 2013–2015 in Sarem Hospital, Tehran, Iran. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for glycoprotein IIIa (PLA1/PLA2), KDR (Q472H), and β-fibrinogen (-455G/A); tetra-primer amplification refractory mutation system (ARMS)-PCR for glycoprotein Ia (807c/t) and vascular endothelial growth factor (VEGF) (2578c/a), and ins/del PCR for angiotensin I-converting enzyme (ACE) (intron 16 I/D). The association between the frequency of the genotypes and RPL was determined by Chi-square and Fisher’s exact tests. Results: The results of the present study revealed a significant relationship between glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms and RPL (P=0.00, 0.02, and 0.00, respectively). In contrast, no relationship was observed between β-fibrinogen (-455G/A), KDR (Q472H), and glycoprotein IIIa (PLA1/PLA2) polymorphisms and increased risk of RPL (P>0.05). Conclusion: This study demonstrated that glycoprotein Ia (807C/T), VEGF (2578C/A), and ACE (intron 16 I/D) polymorphisms may be a risk factor for the women with a history of RPL.

An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease.

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis.

The relationship between polymorphism of the angiotensin I converting enzyme (ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p > 0.05 in each model). In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919–5.093, p < 0.001; recessive, OR = 3.326, 95% CI = 2.190–5.050, p < 0.001) but not in the Caucasian population (p > 0.05 in each model). In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample.

Importance of ACE polymorphisms for endurance performance

The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I- converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. The ACE DD genotype is associated with increased circulating ACE levels, which are generally two times as high as those found for II genotypes. Although most reports suggest that the I allele predisposes to human endurance (1) the literature also contains some opposite data (2). These inconsistencies from genetic association studies relating to the ACE gene and its I/D polymorphism maybe attributable, partially, to epigenetic factors that have been reported to influence ACE activity. Indeed, if both copies of the ACE D/D gene are transiently methylated, ACE increased levels associated with this polymorphism, may be down-regulated. However, there have not been any reports that address whether epigenetic regulation of the ACE gene is specifically involved in modifying human endurance, but, importantly, the human ACE gene promoter has been shown to harbor CpG islands. It is well established that environmental factors may modify the epigenetic profile and that nutrition training, muscle unloading and mechanical stimulation significantly impact on performance, playing an epigenetic role . Hence, it is conceivable that some of these factors might influence the CpG islands within the ACE promoter affecting its expression. The present study is aimed at modulating the epigenetic pattern of the ACE promoter by administering arginine to professional soccer players. ACE (DD, ID, and II) will be genotyped by PCR, then the epigenetic profile of ACE (gene promoter methylation) will be determined by bisulfite method, the serum levels of angiotensin 2 will be measured by ELISA. Hence, we compare the performance capacity of soccer players exhibiting different ACE polymorphisms, by strength, speed, and endurance tests. Subsequently, we will split the subjects under study in 2 groups: group 1 will follow a mediterrean diet, group 2 will follow the same mediterrean diet supplemented with arginine. After six months we will analyze if an epigenetic regulation of the ACE gene has occurred, modulating endurance performance.

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.

ACE polymorphism and use of ACE inhibitors: effects on memory performance

Memory is an important cognition function, being fundamental to the development and independence of individuals. Our aim was to investigate the influence apolipoprotein E (APOE) and angiotensin I-converting enzyme (ACE) polymorphism and ACE inhibitors use, besides their interaction on memory performance of healthy subjects over 50 years. The sample consisted of 205 subjects assessed for five types of episodic memory, using Wechsler Memory Scale-Revised (WMS-R), who answered a questionnaire about drug use and were assessed for the ACE insertion/deletion polymorphism and APOE polymorphism. We found no influence of the APOE gene. The use of ACE inhibitors beneficially influenced learning ability scores (p = 0.02). Besides, I allele carriers of ACE polymorphism showed higher verbal memory scores compared with homozygous DD. Also, we observed an interaction influencing learning ability between the ACE polymorphism and the use of inhibitors, the beneficial influence of the I allele was present only in individuals who make use of ACE inhibitors. We conclude that the ACE gene has influence on memory performance, and that this influence is modulated by ACE inhibitors use.

Frequency of APOE, MTHFR and ACE polymorphisms in the Zambian population

BackgroundPolymorphisms within the apolipoprotein-E (APOE), Methylenetetrahydrofolate reductase (MTHFR) and Angiotensin I-converting enzyme (ACE) genes has been associated with cardiovascular and cerebrovascular disorders, Alzheimer’s disease and other complex diseases in various populations. The aim of the study was to analyze the allelic and genotypic frequencies of APOE, MTHFR C677T and ACE I/D gene polymorphisms in the Zambian population.ResultsThe allele frequencies of APOE polymorphism in the Zambian populations were 13.8%, 59.5% and 26.7% for the ε2, ε3 and ε4 alleles respectively. MTHFR C677T and ACE I/D allele frequencies were 8.6% and 13.8% for the T and D minor alleles respectively. The ε2ε2 genotype and TT genotype were absent in the Zambian population. The genetic distances between Zambian and other African and non-African major populations revealed an independent variability of these polymorphisms.ConclusionWe found that the APOE ε3 allele and the I allele of the ACE were significantly high in our study population while there were low frequencies observed for the MTHFR 677 T and ACE D alleles. Our analysis of the APOE, MTHFR and ACE polymorphisms may provide valuable insight into the understanding of the disease risk in the Zambian population.

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 impact of renin–angiotensin system, angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran

IntroductionSeveral proteins of renin–angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer. Materials and methodsThe I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009. Genomic DNA was extracted from a Formalin-Fixed Paraffin-Embedded (FFPE) tissue of breast cancer sample blocks. All the potential clinical and pathological prognostic variables were analyzed to establish the impact of I/D and A1166C polymorphisms on disease-free and overall survival rates. Disease-free and overall survival rates were the primary endpoints of the study. ResultsThe ACE (I/D) polymorphism was associated with 3-year disease-free survival. Disease-free survival in DD carriers was significantly increased compared to ID plus II carriers (HR=4.75; 95% CI, 1.39–16.24; p=0.013). No significant association was found between AGTR1 (A1166C) and 3-year disease-free survival (p=0.233). Also, the ACE (I/D) and AGTR1 (A1166C) polymorphisms were not associated with breast cancer overall survival. ConclusionThe ACE (I/D) polymorphism was associated with 3-year disease-free survival of the women with breast cancer. Besides, disease-free survival in DD carriers was significantly increased compared to ID plus II carriers.

Effects of ACE polymorphisms and other risk factors on the severity of coronary artery disease

Coronary artery disease (CAD) is a multifactorial disease influenced by genetic and environmental factors. Major risk factors of CAD are hypertension, hyperlipidemia, smoking, family history and obesity. Also polymorphisms in the angiotensin-I converting enzyme (ACE) gene can associate with CAD. The relationship between ACE polymorphisms and other risk factors is not well understood in CAD, likely due to the complex interrelation of genetic and environmental risk factors. The aim of this study was to investigate the associations of CAD risk factors and ACE polymorphisms in patients with CAD. We enrolled 203 consecutive patients and 140 healthy subjects in the study. The severity of CAD was evaluated according to the number of vessels with significant stenosis. ACE insertion (I)/deletion (D) genotype was determined by PCR. The frequency of the DD genotype was significantly higher in patients. D allele frequency was higher among CAD subjects when compared to the control group. The number of stenotic vessels were found to be statistically associated with a high frequency of DD polymorphism and D allele and a low frequency of I allele in patients, especially in male patients. The control group displayed II and ID genotypes more frequently than did the patients. The ACE I/D genotype was associated with hyperlipidemia and smoking history. We consider that the DD polymorphism and D allele may affect the severity of CAD, while I allele may have a protective effect. In conclusion, the ACE I/D genotype may interact with conventional risk criteria in determining the risk of CAD.

The insertion/deletion polymorphism in the ACE gene and chronic obstructive pulmonary disease

An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.

Association of Angiotensin I Converting Enzyme Polymorphism as Genetic Risk Factor in Benign Prostatic Hyperplasia and Prostate Cancer

Angiotensin I converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is one of the genetic factors found to be related with prostate cancer (PC). We investigated the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, prediagnostic plasma prostate specific antigen (PSA) levels, and PC risk with I/D polymorphism of the ACE gene. We recruited 206 subjects in this study, including 95 patients with PC and 111 patients with benign prostatic hyperplasia. The odds ratio between II and DD polymorphisms (reference) was 1.38. It means that the presence of the II polymorphism increased the risk of cancer more than 38% compared with DD polymorphism although still it was not statistically significant. The mean of total PSA in the patients with the II genotype was 20 ng/L more than that in those who had DD polymorphism. The odds ratio (OR) between the D allele and PC development was 1.16, indicating that this allele increased the risk of cancer about 16%. We found no association between the ACE polymorphism and cancer risk, overall or by grade, stage, or age of diagnosis. The difference in results for ACE polymorphisms between studies may be minimized by using larger study groups.

The Alu polymorphism of angiotensin I converting enzyme (ACE) and atherosclerosis, incident chronic diseases and mortality in an elderly Chinese population.

We examined the contribution of ACE I/D polymorphism in a large Chinese population to four year change in ankle-brachial index (ABI), development of cardiovascular diseases and mortality in a prospective study adjusting for many confounding factors. Data are drawn from a longitudinal study of 4000 community-living men and women aged 65 years and over, for which detailed information regarding lifestyle, chronic diseases, body mass index (BMI), ABI measurements and ACE polymorphisms were documented at baseline. During the fifth year of follow up, incident cardiovascular diseases, ABI, and mortality were documented, and related to ACE genotype adjusting for age, smoking, alcohol, dietary intake, physical activity, body mass index, and use of ACE inhibitors. Women with the D/D genotype had the greatest reduction in mean ABI after adjusting for confounding factors. D/D genotype was also more common among women who developed hypertension or myocardial infarction. However D/D genotype was associated with mortality only in men. In a Chinese elderly population, ACE polymorphism may be considered "deleterious" to longevity, the D/D genotype being associated with mortality, the atherosclerotic process, hypertension and myocardial infarction. There are gender differences in the relationship between D/D genotype and cardiovascular diseases and mortality may not be mediated by the atherosclerotic process alone.

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.

Association of Angiotensin Converting Enzyme (Insertion/Deletion) Gene Polymorphism with Essential Hypertension in Northern Indian Subjects

Essential hypertension is a multifactorial disease in which genetic and environmental factors play an important role. The renin-angiotensin system (RAS) is known to play a critical role in the homeostasis of blood pressure. Angiotensin-I converting enzyme (ACE) is a significant component of RAS, and an insertion/deletion (I/D) polymorphism in its gene has been implicated in predisposition to hypertension. The purpose of the current study is to investigate the association of I/D polymorphism of the ACE gene with essential hypertension in northern Indians. Two hundred twenty-two patients with essential hypertension and 252 controls were recruited for the study. DNA samples were isolated from peripheral blood by using a kit. Polymerase chain reaction was used for genotyping. All the genotypes and allele distribution in study subjects were in the Hardy-Weinberg equilibrium. There was a significant difference in the distribution of DD, II, and ID genotypes of ACE polymorphism in patients and controls. In the subjects having an I allele, the odds ratio is 2.08 [1.6-2.58] at 95% confidence interval, thus suggesting an association of ACE I/D gene polymorphism with essential hypertension. Our findings suggest that the I allele of ACE I/D polymorphism is associated with essential hypertension in our population.

The association between ACE polymorphism and risk of colorectal cancer in a Chinese population

Objectives Angiotensin I-converting enzyme (ACE) plays crucial roles not only in the regulation of circulatory homeostasis but also in the pathology of carcinomas. An insertion–deletion (I/D) polymorphism in intron 16 of ACE gene was identified to be functional. We aimed to investigate the association between ACE I/D polymorphism and risk of colorectal cancer (CRC). Design and methods Using genomic DNA from 241 CRC patients and 299 control subjects, we genotyped the ACE I/D polymorphism using a polymerase chain reaction analysis. Results We found that patients carrying the D allele were associated with an increased risk of developing poorly differentiated cancer and metastasis compared with those carrying the I allele (OR = 1.54, 95%CI, 1.04–2.28; OR = 1.56, 95%CI, 1.08–2.26, respectively), although no significant association was observed between cases and controls in overall analysis. Conclusions These findings indicate that the ACE I/D polymorphism is likely to play a role in CRC progression.

Association of angiotensin I converting enzyme, angiotensin II type 1 receptor and angiotensin I converting enzyme 2 gene polymorphisms with the dyslipidemia in type 2 diabetic patients of Chinese Han origin.

To investigate whether the genetic polymorphisms in the angiotensin I converting enzyme (ACE) (insertion/ deletion, or I/D), angiotensin II type 1 receptor (AT1R) (rs5186), and ACE2 (rs2285666) could be associated with dyslipidemia in Type 2 diabetic (T2D) patients of Chinese Han origin. The above 3 polymorphisms were genotyped in a total of 282 patients with T2D and dyslipidemia (Group A), 182 patients with T2D but without dyslipidemia (Group B), and 324 healthy controls. The association between a certain polymorphism and each group was assessed by an odds ratio (OR). The D allele of the ACE (I/D) was significantly associated with the risk of T2D accompanying dyslipidemia between group A and controls [OR=1.37, 95% confidence interval (CI)=1.08-1.74; p=0.010], and significant association of the D allele with dyslipidemia was also observed in diabetic patients (OR=1.88, 95% CI=1.40-2.54; p<0.001). Furthermore, the ID genotype had a decreased risk of developing T2D without dyslipidemia as compared with controls (OR=0.52, 95% CI=0.32-0.82; p=0.0060). The distributions of the AT1R (rs5186) and ACE2 (rs2285666) genotypes and alleles did not differ between T2D patients with or without dyslipidemia and the controls. This study demonstrates that the ACE (I/D) polymorphism is associated with T2D, regardless of the absence or presence of dyslipidemia. The polymorphisms in the AT1R (rs5186) and ACE2 (rs2285666) seem to play lesser roles in the development of T2D.

Relationship of Physical Activity and Angiotensin I-Converting Enzyme Polymorphism on Cardiovascular Disease Risk Factors in Young Adults

Relationship of Physical Activity and Angiotensin I-Converting Enzyme Polymorphism on Cardiovascular Disease Risk Factors in Young Adults