The Influence of Angiotensin Converting Enzyme and Angiotensinogen Gene Polymorphisms on Hypertrophic Cardiomyopathy

Some studies have reported that angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes have been associated with hypertrophic cardiomyopathy (HCM). However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included “hypertrophic cardiomyopathy”, “angiotensin converting enzyme” (ACE) or “ACE” and “polymorphism or mutation”. For the association of AGT M235T polymorphism and HCM, “angiotensin converting enzyme” or “ACE” was replaced with “angiotensinogen”. A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05) after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D gene polymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D gene polymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.     

ACE I/D gene polymorphism can't predict the steroid responsiveness in Asian children with idiopathic nephrotic syndrome: a meta-analysis

Background

The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness.

Methodology/Principal Findings

Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2010, and eligible investigations were synthesized using meta-analysis method. Five investigations were identified for the analysis of association between ACE I/D gene polymorphism and steroid-resistant nephrotic syndrome (SRNS) risk in Asian children and seven studies were included to explore the relationship between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) susceptibility. Five investigations were recruited to explore the difference of ACE I/D gene distribution between SRNS and SSNS. There was no a markedly association between D allele or DD genotype and SRNS susceptibility or SSNS risk, and the gene distribution differences of ACE between SRNS and SSNS were not statistically significant. II genotype might play a positive role against SRNS onset but not for SSNS (OR = 0.51, P = 0.02; OR = 0.95, P = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable.

Conclusions/Significance

Our results indicate that D allele or DD homozygous can''t become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS.     

Association of angiotensin-converting enzyme I/D polymorphism with heart failure: a meta-analysis

Heart failure (HF) is a complex clinical syndrome and is thought to have a genetic basis. Numerous case-control studies have investigated the association between heart failure and polymorphisms in candidate genes. Most studies focused on the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism, however, the results were inconsistent because of small studies and heterogeneous samples. The objective was to assess the association between the ACE I/D polymorphism and HF. We performed a meta-analysis of all case-control studies that evaluated the association between ACE I/D polymorphism and HF in humans. Studies were identified in the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Two reviewers independently assessed the studies. Seventeen case-control studies with a total of 5576 participants were included in the meta-analysis, including 2453 cases with HF and 3123 controls. The heterogeneity between studies was significant. No association was found under all the four genetic models (D vs. I, DD vs. ID and II, DD and ID vs. II, DD vs. ID). Subgroup analyses for ischemic HF (IHF) and HF because of dilated cardiomyopathy (DHF) also showed no significant association between ACE I/D polymorphism and HF. No significant association between the ACE I/D polymorphism and risk of HF was found in this meta-analysis. The future studies should focus on large-scale prospective and case-control studies which designed to investigate gene-gene and gene-environment interactions to shed light on the genetics of HF.     

Association between Angiotensin I-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of Kidney Transplantation: A Meta-Analysis

PurposeAngiotensin I-converting enzyme (ACE) is crucial in the renin–angiotensin–aldosterone system. ACE insertion/deletion (I/D) polymorphism is a common genetic variation of this gene and is associated with several disease phenotypes. However, the results of published studies on the influence of this polymorphism on renal transplantation are inconsistent. Therefore, a meta-analysis was performed to evaluate the association between ACE I/D polymorphism and prognosis of kidney transplantation.MethodsA meta-analysis was performed based on 21 case–control studies from 12 publications (1497 cases and 2029 controls) and 10 studies with quantitative values from 5 publications (814 patients). Pooled odds ratios (ORs) and weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were used to estimate associations.ResultsACE I/D polymorphism was found to be associated with acute rejection (AR) in genotypes DD+ID versus II (OR = 1.62, 95% CI = 1.14–2.29) and with serum creatinine concentration after renal transplantation in genotypes DD versus ID (WMD = 13.12, 95% CI = 8.09–18.16). Stratified analysis revealed that recipients transplanted within a year had higher serum creatinine concentrations in the DD versus ID model. No significant association was found between hypertension and ACE I/D polymorphism.ConclusionACE I/D polymorphism is associated with AR and allograft function after kidney transplantation.     

Angiotensin-converting enzyme and cardiovascular disease risk.

The published studies of the association of the angiotensin-converting enzyme (ACE) genotype with cardiovascular disease have used many different diagnostic criteria for cardiovascular disease and have drawn their samples from different patient groups and different populations. This review examines the association of the ACE DD genotype with cardiovascular disease risk in studies grouped by their case criterion, the geographical region of the population samples, and by the cardiovascular risk level of the patient sample. In studies where the underlying odds ratios are determined to be homogeneous, the overall odds ratios for myocardial infarction and coronary artery disease with regard to the ACE DD genotype are estimated using the Mantel-Haenszel method.     

Association of ACE I/D polymorphism with cardiovascular risk factors

Since the identification of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene, the D allele has been recognized to be associated with cardiovascular disease. Moreover, significant associations of this polymorphism with multiple cardiovascular risk factors have been reported, although some studies failed to detect such associations. In the present study, we investigated the association of the ACE gene polymorphism with the parameters of multiple risk factors in 300 Japanese men who participated in a medical check-up. This investigation detected a significant association of the polymorphism with systolic blood pressure (P=0.007) and diastolic blood pressure (P=0.026), with their highest values in DD subjects and lowest values in II subjects. This significant association is consistent with the proposition that the polymorphism influences blood-pressure variability in men. Furthermore, we investigated the association of the polymorphism with four major disorders (obesity, hyperlipidemia, hypertension, diabetes mellitus) correlated with the risk for cardiovascular disease in the same 300 subjects. This investigation failed to detect any significant association of the polymorphism with each disorder. However, there was a trend that all four disorders were more frequent in ID and DD subjects than in II subjects. We therefore analyzed the association between the ACE gene polymorphism and having at least one of the four disorders in the same population. This analysis detected a significant difference: that ID and DD subjects had at least one of the four disorders more frequently than II subjects (P=0.008; odds ratio=1.89, 95% confidence interval= 1.19-2.99). Taken together, the results of this study are compatible with the proposition that the ACE polymorphism is associated with cardiovascular disease partially mediated through the four disorders in our population.     

Effect of rs4646994 polymorphism of angiotensin-converting enzyme on the risk of nonischemic cardiomyopathy

Background: Angiotensin-converting enzyme (ACE) gene polymorphisms have recently been shown to be associated with risk of developing left ventricular hypertrophy (LVH). However, the results were controversial. We aimed to conduct this meta-analysis to further confirm the association between ACE rs4646994 polymorphism and hypertrophic cardiomyopathy (HCM)/dilated cardiomyopathy (DCM).Methods: PubMed, Embase, the Chinese National Knowledge Information, and Wanfang databases were searched for eligible studies. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of included studies. Then we evaluated the association between ACE gene mutation and HCM/DCM by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analysis was further performed to explore situations in specialized subjects. Sensitivity analysis and publication bias was assessed to confirm the study reliability.Results: There were 13 studies on DCM (2004 cases and 1376 controls) and 16 studies on HCM (2161 controls and 1192 patients). ACE rs4646994 polymorphism was significantly associated with DCM in all genetic models. However, in HCM, four genetic models (allele model, homozygous model, heterozygous model, and dominant model) showed significant association between ACE rs4646994 polymorphism and DCM. In subgroup analysis, we found that ACE rs4646994 polymorphism was significantly associated with DCM/HCM in Asian population. Finally, we also conducted a cumulative meta-analysis, which indicates that the results of our meta-analysis are highly reliable.Conclusion: ACE rs4646994 polymorphism increases the risk of DCM/HCM in Asians, but not in Caucasians. More case–control studies are needed to strengthen our conclusions and to assess the gene–gene and gene–environment interactions between ACE rs4646994 polymorphism and DCM/HCM.     

Deletion polymorphism of the angiotensin I-converting enzyme gene in elderly patients with coronary heart disease

Controversy exists as to whether the deletion/deletion (DD) genotype of angiotensin l-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD). There are only a few studies dealing with this issue in the elderly, also with controversial results. The aim of this study was the assessment of correlation between genetic markers and the risk of CHD in the elderly. The results indicated DD genotype importance for CHD in the elderly as proven by discriminant analysis (chi2 = 25.77; df = 16; p = 0.0620). However, the use of univariate method demonstrated no correlation between DD genotype of ACE gene polymorphism and coronary artery disease. D allele of ACE gene was associated with higher activities of ACE plasma. A weak, but increased risk of MI is associated with high frequency of DD genotype in the elderly. Strong correlation between ACE polymorphism and ACE plasma activities was demonstrated.     

Influence of the Angiotensin Converting Enzyme Insertion or Deletion Genetic Variant and Coronary Restenosis Risk: Evidence Based on 11,193 Subjects

The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin converting enzyme is a controversial risk factor for restenosis after percutaneous transluminal coronary angioplasties (PTCA) in patients. Genetic association studies can be problematic to reproduce due to insufficient power, phenotypic heterogeneity, population stratification, small effect of the variant and even publication biases. To derive a more precise estimation of the relationship as well as to quantify the between-study heterogeneity and potential bias, a meta-analysis including 11,193 patients from 33 published cohort studies was performed. In a combined analysis, the summary per-allele odds ratio for restenosis was 1.31 (95% CI: 1.08-1.58, P = 0.006), and 1.22 (95% CI: 0.95-1.56, P = 0.12), for PTCA-stent and PTCA-balloon, respectively. In the subgroup analysis by ethnicity, significantly increased restenosis risks after PTCA-stent were found in Asians for the polymorphism; whereas no significant associations were found among Caucasians. As for restenosis risks after PTCA-balloon, no evidence of any gene-disease association was obtained in the stratified analyses according to ethnicity and study size. In conclusion, this meta-analysis demonstrated that the DD homozygous of ACE I/D polymorphism was significantly associated with elevated restenosis susceptibility after PTCA-stent among Asian populations.     

The association of rs1149048 polymorphism in Matrilin-1(MATN1) gene with adolescent idiopathic scoliosis susceptibility: a meta-analysis

Several previous studies have evaluated the association between rs1149048 polymorphism in the matrilin-1 gene (MATN1) and the risk of adolescent idiopathic scoliosis (AIS). However the results of those studies were inconsistent. We conducted this meta-analysis to assess whether rs1149048 polymorphism was involved in the risk of AIS and evaluated the associations in different ethnicities. Electronic databases, such as: PubMed, EMBASE, WANFANG databases in any languages up to Dec 2012 were searched to assess the association between rs1149048 polymorphism and AIS. Meta-analysis was performed by STATA 12.0 software to estimate the pooled odds ratio (OR) and the 95 % confidence interval (CI). Finally four papers including five studies which involved 1436 AIS patients and 1,879 controls were identified for this meta-analysis. The results showed that G allele of the rs1149048 was significantly associated with increased AIS risk [OR = 1.13, 95 % CI (1.02–1.25), P = 0.023]. As for genotype (GG vs. GA + AA), homozygous GG genotype was also found to be a risk factor of developing AIS. The subgroup meta-analysis results showed G allele and GG genotype were significantly associated with AIS in Asian group but not in Caucasian group. Neither Egger’s test nor Begg’s test found evidence of publication bias in current study (P > 0.05). In summary, this meta-analysis found an overall significant association of rs1149048 polymorphism with risk of AIS, especially in Asian population. The relationship between rs1149048 polymorphism and AIS in other ethnic population is needed to be investigated.     

ACE ID genotype affects blood creatine kinase response to eccentric exercise.

Unaccustomed exercise may cause muscle breakdown with marked increase in serum creatine kinase (CK) activity. The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism and tissue injury. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. We hypothesized that ACE ID genotype may contribute to the wide variability in individuals' CK response to a given exercise. Young individuals performed maximal eccentric contractions of the elbow flexor muscles. Pre- and postexercise CK activity was determined. ACE genotype was significantly associated with postexercise CK increase and peak CK activity. Individuals harboring one or more of the I allele had a greater increase and higher peak CK values than individuals with the DD genotype. This response was dose-dependent (mean +/- SE U/L: II, 8,882 +/- 2,362; ID, 4,454 +/- 1,105; DD, 2,937 +/- 753, ANOVA, P = 0.02; P = 0.009 for linear trend). Multivariate stepwise regression analysis, which included age, sex, body mass index, and genotype subtypes, revealed that ACE genotype was the most powerful independent determinant of peak CK activity (adjusted odds ratio 1.3, 95% confidence interval 1.03-1.64, P = 0.02). In conclusion, we indicate a positive association of the ACE ID genotype with CK response to strenuous exercise. We suggest that the II genotype imposes increased risk for developing muscle damage, whereas the DD genotype may have protective effects. These findings support the role of local RAS in the regulation of exertional muscle injury.     

ACE基因多态性与高血压肾脏损害及PAI-1的关系

为探讨血管紧张素转换酶（ACE）基因多态性与高血压肾损害和纤溶酶原激活物抑制物-1（PAI-1）的关系,应用聚合酶链反应（PCR）检测96例正常人、67例高血压无肾脏损害患者和70例高血压伴肾损害患者的ACE基因型,采用ELISA法检测血浆PAI-1。ACE基因I/D多态性与高血压病无明显相关,但高血压肾损害患者DD基因型频率及D等位基因频率显著高于对照组和高血压无肾脏损害组,χ2值分别为6.8589、5.6162 和5.9085、5372。血浆PAI-1在DD型、ID型、II型高血压患者之间亦有显著性差异（P＜0.05）。ACE基因DD型可能是高血压肾损害的危险因素;ACE基因多态性与血浆PAI-1水平相关。 Abstract:The work is to explore the relationship between the polymorphism of angiotensin converting enzyme(ACE) gene and hypertensive kidney lesion/PAI-1 in hypertension patients.ACE genotyping with polymorase chain reaction (PCR) was performed in 96 unrelated healthy controls,67 hypertensives without kidney lesion and 70 hypertensives complicated with kidney lesion.The plasma PAI-1 were determined with ELISA.No significant differences could be detected between ACE gene I/D polymorphism and hypertension.However,the frequencies of DD genotype and deletion allele among the hypertensives complicated with kidney lesion were higher than those among the healthy controls and those among the hypertensives without kidney lesion."χ2" values were 6.8589,5.6162 and 5.9085,5.372 respectively.The plasma PAI-1 level showed significant differences among DD genotype,ID genotype and II genotype(P＜0.05).The DD genotype of ACE gene may be a risk for hypertensive kidney lesion.The plasma PAI-1 level is associated with ACE gene polymorphism.     

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84unrelated NIDDM patients with a known disease duration of less than 1year and in 115age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and Ialleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2 ± 2.4, 9.2 ± 4.0, and 10.7 ± 2.7mmol/l · h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the nondiabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the Dallele and vascular complications in NIDDM. Received: 15 September 1997 / Accepted: 13 November 1997     

Angiotensin converting enzyme gene polymorphism and traditional Sasang classification in Koreans with cerebral infarction

Sasang constitutional medicine is a major branch of Korean traditional oriental medicine. Constitutions of Sasang medicine refer to Taeyangin, Taeumin, Soyangin, and Soumin. The differences of disease severity to be shown in the constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction, CI, angiotensin converting enzyme (ACE) gene polymorphism, and Sasang constitutional classification. We investigated the association between ACE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang constitutional medicine. 208 CI patients and 643 controls without CI were examined. ACE genotype was determined by 7.5 % polyacrylamide gel separation after DNA amplification. The ACE/DD genotype was not associated with CI. The frequency of Taeumin of Sasang constitutional medicine in patients with CI was significantly higher than that in controls (chi2=41.202, p<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with ACE/DD genotype. Although we did not find any association between ACE gene polymorphism and CI in Koreans, there were significant differences in allele frequencies between Koreans and Europeans, but not Japanese and Chinese populations. Furthermore, we first attempted to evaluate the efficacy of Sasang constitutional medicine, and to find an association with CI.     

Angiotensin-converting enzyme insertion/deletion polymorphism and risk of myocardial infarction in an updated meta-analysis based on 34 993 participants

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and risk of myocardial infarction (MI) has been extensively studied. However, the results were in controversy. This study aimed to explore the association between ACE I/D polymorphism and risk of MI by using a meta-analysis. We retrieved the following databases to indentify eligible studies: Medline, Embase, ISI, VIP, CBM and Wan Fang database. The latest update was 10th May, 2012. Odds ratio and 95% confidence interval (95% CI) were used to present the strength of the association. A total of 40 case–control studies with 34 993 participants were included. Overall, D allele of ACE I/D polymorphism was significantly associated with an increased risk of MI in genetic comparison models (OR (95% CI): 1.41 (1.22–1.64) for DD vs. II; 1.11 (1.01–1.21) for ID vs. II; 1.23 (1.10–1.37) for D carriers vs. II; 1.28 (1.15–1.43) for DD vs. I carriers and 1.06 (1.02–1.10) for D carriers vs. I carriers). Subgroup analyses, according to ethnicities and countries of participants also indicated that D allele was significantly associated with an increased risk of MI in Asians (especially for Chinese) and Caucasians (especially for English, French, Germans and Italians) (OR (95% CI) of DD vs. ID + II: 2.11 (1.65–2.70) for Asians and 1.15 (1.05–1.27) for Caucasians). In conclusion, this meta-analysis indicated that D allele of ACE I/D polymorphism was a possible risk factor for MI incidence for both Asians and Caucasians.     

ACE I/D polymorphism in Alzheimer’s disease

Angiotensin-converting enzyme (ACE) has been reported to show altered activity in patients with neurological diseases. The recent studies found that a 287 bp insertion/deletion (I/D) polymorphism of the ACE gene may be associated with susceptibility to Alzheimer’s disease (AD) but the results have been heterogenous between studies in Europe. In the present study we examined for the first time the association of ACE I/D polymorphism along with APOE genotype in 70 sporadic AD and 126 control subjects in Slovak Caucasians (Central Europe). An increased risk for AD was observed in subjects with at least one APOE*E4 allele (OR=3.99, 95% CI=1.97–8.08). No significant differences for the genotype distribution or the allele frequency were revealed comparing controls and patients for ACE gene. Gene-gene interaction analysis showed increase of the risk to develop AD in subjects carrying both the ACE DD genotype and the APOE*E4 allele (OR=10.32, 95% C.I. 2.67–39.81).     

Angiotensin converting enzyme gene polymorphism and myocardial infarction a large association and linkage study

The DD genotype of the angiotensin converting enzyme (ACE) polymorphism has been associated with myocardial infarction (MI). However, sample sizes of many case-control studies showing positive association were small and data were inconsistent. Furthermore, no family-based study is available.In a case-control study frequencies of the ACE genotypes were compared in 1319 unrelated patients with previous MI before 60 years of age (616 from the MONICA Augsburg region and 703 from rehabilitation centers in south Germany) and in 2381 population controls from the MONICA Augsburg study region). Furthermore, linkage and association of the ACE I/D polymorphism with MI were tested in 246 informative families using the sib-transmission/disequilibrium test (S-TDT).Overall, no excess of the D allele was found in MI patients (frequency 0.53 versus 0.57 in the general population; P=0.2). The ACE DD genotype was even slightly less frequent in groups with MI compared to the general population controls (0.26 versus 0.33 in women and 0.28 versus 0.33 in men). Similar results were also obtained in 247 men with low cardiovascular risk. In the family-based study, the frequency of the D allele was not different in siblings with or without previous MI (0.53 versus 0.50, respectively; S-TDT P=0.15) indicating no linkage or association of the D allele with MI.In a case-control study of MI patients and controls from the general population as well as a family study neither association nor linkage of the ACE D allele with MI was detected despite sample sizes that were among the largest samples studied so far.     

Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis

Background

A number of studies have reported an association of angiotensin-converting enzyme (ACE) gene polymorphism with primary intracerebral hemorrhage (PICH), however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH.

Methods

PubMed and Embase databases (through Dec 2012) were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs) were estimated and potential sources of heterogeneity and bias were explored.

Results

A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07–2.35 for DD vs. DI+II). However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16–2.66 for DD vs. DI+II), but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36–3.88, P = 0.784 for DD vs. DI+II). The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models.

Conclusions

These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.     

Insertion/deletion polymorphism of angiotensin-converting enzyme gene--risk factor for coronary artery disease in the Tuzla region population (Bosnia and Herzegovina)

Angiotensin II is the major effector molecule of renin-angiotensin system; its production can be conveniently interrupted by angiotensin-converting enzyme (ACE). Typical plasma levels of ACE accompany the I/D polymorphism; however, a controversy exists as to whether the DD genotype of the ACE polymorphism affects the risk for the development of coronary artery disease (CAD) and to what extent the ACE polymorphism is associated with CAD in different populations. We compared the I/D polymorphism in 212 CAD patients younger than 50 years with 165 healthy control individuals. They were all from the Tuzla region in Bosnia and Herzegovina. Patients with CAD had a higher prevalence of the DD genotype (36.3%) than controls (25.6%). The odds ratio for the ACE DD genotype in CAD patients was 1.7 (95% confidence interval 1.0-2.7; p < 0.05). We may conclude that the D/D genotype of the ACE gene polymorphism is associated with an increased risk for CAD in the Bosnian population.     

Prevalence of the Angiotensin I Converting Enzyme Gene Insertion/Deletion Polymorphism in a Healthy Turkish Population

Angiotensin converting enzyme (ACE) plays an essential role in the renin–angiotensin system. It converts angiotensin I to angiotensin II and inactivates bradykinin and tachykinins. Numerous studies have been published investigating associations of the ACE gene I/D polymorphism with various pathophysiological conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of healthy volunteers from western Turkey, including 1063 healthy Turkish controls. Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2% for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1% for the D allele. This study demonstrates that the allele and genotype frequency values for the Turkish population are similar to previously published frequencies for Caucasian populations.