The initial report of an association of the ACE I/D polymorphism and restenosis after angioplasty was based on a rather small sample of only 82 Japanese patients [20]. heterogeneity and publication bias. Results A total of 33 cohort studies involving 11,099 subjects were included. In a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27C2.04; em P /em 10?5). In the subgroup analysis by intervention, significantly increased risks were also found in PTCA-stent and PTCA-balloon for the DD genotype of the polymorphism. Conclusions Our meta-analysis showed that this DD genotype of ACE I/D polymorphism was significantly associated with increased risk of restenosis, particularly for PTCA-stent. Introduction Coronary artery disease (CAD), including its most severe complication, myocardial infarction (MI), is the leading cause of morbidity and mortality worldwide. Percutaneous transluminal coronary angioplasties (PTCA) is now a well established treatment for widening the lumen of coronary arteries stenosed by atherosclerotic lesions. The main limitation of PTCA is usually restenosis in 30C40% of patients, typically occurring between 1C3 months [1], [2]. A number of clinical and angiographic variables, including advanced age, diabetes mellitus, hyperlipidaemia, hypertension, unstable angina, severe coronary artery stenosis and long lesions, have been reported to be associated with an increased risk of restenosis after PTCA [3]C[6]. However, only 30% of restenosis could be predicted Balapiravir (R1626) from clinical and angiographic variables [5]. The hypothesis of a genetic susceptibility to explain the 30% to 40% of patients affected by restenosis has been raised. Inappropriate activation of the reninCangiotensin system may play a part in the development of many cardiovascular disorders [7], [8]. Experimental studies favor the major role of the renin angiotensin system (RAS) in vessel healing after PTCA [9]C[11]. A common insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has been reliably associated with substantial differences in the plasma and tissue angiotensin-converting enzyme (ACE) activity in a codominant fashion not only in persons of European descent, but also in other populations such as Hispanics [12]C[14]. Individuals carrying the D allele have higher ACE activity, which has been proposed as an intermediate phenotype of potential relevance for the development of high blood pressure and subclinical atheroma (i.e., higher intima-media thickness of the carotid artery) [13], [15]. It has been suggested that this incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with the angiotensin converting enzyme DD genotype (which is usually associated with particularly high plasma angiotensin converting enzyme levels) than in others. However, these studies have yielded apparently conflicting results. These disparate findings may be partly due to insufficient power, false-positive results, and publication biases. The interpretation of these studies has been further complicated by the use of different populations. We therefore performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between ACE I/D polymorphisms and post-PTCA restenosis risk. Materials and Methods Literature Search Strategy Electronic databases (Pubmed, EMBASE, ISI Web of Science, EBSCO, Cochrane Library databases and CNKI) were searched up to March 2013 for all those genetic association studies evaluating the ACE-I/D polymorphism and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) in humans in all languages. The search strategy contained both medical subject heading terms and text words as follows: angiotensin-converting enzyme or ACE or peptidyl-dipeptidase A, in combination with angioplasty or stent or balloon or stenting or percutaneous or PTCA, and combined with genetic or polymorphism(s) or variations(s).In total, the meta-analysis involved 33 studies for restenosis which provided 11,099 subjects. The combined evidence suggested that ACE DD genotype did contribute to the development of post-PTCA restenosis. and CNKI were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias. Results A total of 33 cohort studies involving 11,099 subjects were included. In a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27C2.04; em P /em 10?5). In the subgroup analysis by intervention, significantly increased risks were also found in PTCA-stent and PTCA-balloon for the DD genotype of the polymorphism. Conclusions Our meta-analysis showed that the DD genotype of ACE I/D polymorphism was significantly associated with increased risk of restenosis, particularly for PTCA-stent. Introduction Coronary artery disease (CAD), including its most severe complication, myocardial infarction (MI), is the leading cause of morbidity and mortality worldwide. Percutaneous transluminal coronary angioplasties (PTCA) is now a well established treatment for widening the lumen of coronary arteries stenosed by atherosclerotic lesions. The main limitation of PTCA is restenosis in 30C40% of patients, typically occurring between 1C3 months [1], [2]. A number of clinical and angiographic variables, including advanced age, diabetes mellitus, hyperlipidaemia, hypertension, unstable angina, severe coronary artery stenosis and long lesions, have been reported to be associated with an increased risk of restenosis after PTCA [3]C[6]. However, only 30% of restenosis could be predicted from clinical and angiographic variables [5]. The hypothesis of a genetic susceptibility to explain the 30% to 40% of patients affected by restenosis has been raised. Inappropriate activation of the reninCangiotensin system may play a part in the development of many cardiovascular disorders [7], [8]. Experimental studies favor the major role of the renin angiotensin system (RAS) in vessel healing after PTCA [9]C[11]. A common insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has been reliably associated with substantial differences in the plasma and tissue angiotensin-converting enzyme (ACE) activity in a codominant fashion not only in persons of European descent, but also in other populations such as Hispanics [12]C[14]. Individuals carrying the D allele have higher ACE activity, which has been proposed as an intermediate phenotype of potential relevance for the development of high blood pressure and subclinical atheroma (i.e., higher intima-media thickness of the carotid artery) [13], [15]. It has been suggested that the incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with the angiotensin converting enzyme DD genotype (which is associated with particularly high plasma angiotensin converting enzyme levels) than in others. However, these studies have yielded apparently conflicting results. These disparate findings may be partly due to insufficient power, false-positive results, and publication biases. The interpretation of these studies has been further complicated by the use of different populations. We therefore performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between ACE I/D polymorphisms and post-PTCA restenosis risk. Materials and Methods Literature Search Strategy Electronic databases (Pubmed, EMBASE, ISI Web of Science, EBSCO, Cochrane Library databases and CNKI) were searched up to March 2013 for all genetic association studies evaluating the ACE-I/D polymorphism and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) in humans in all languages. The search strategy contained both medical subject heading terms and text words as follows: angiotensin-converting enzyme or ACE or peptidyl-dipeptidase A, in combination with angioplasty or stent or balloon or stenting or percutaneous or PTCA, and combined with genetic or polymorphism(s) or variations(s) or genotype or gene(s). Eligible Studies and Data Extraction Eligible studies had to meet all of the following criteria: (1) original papers containing independent data which have been published in peer-reviewed journal, (2) genotype distribution information or odds ratio (OR) with its 95% confidence interval (CI) and P-value, (3) restenosis had to be defined as 50% luminal diameter stenosis at follow-up angiography after an initially successful angioplasty procedure, and (4) prospective cohort studies or caseCcontrol studies. The following information was extracted.The interpretation of these studies has been further complicated by the use of different populations. involving 11,099 subjects were included. In a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27C2.04; em P /em 10?5). In the subgroup analysis by intervention, significantly increased risks were also found in PTCA-stent and PTCA-balloon for the DD genotype of the polymorphism. Conclusions Our meta-analysis showed that the DD genotype of ACE I/D polymorphism was significantly associated with increased risk of restenosis, particularly for PTCA-stent. Introduction Coronary artery disease (CAD), including its most severe complication, myocardial infarction (MI), is the leading cause of morbidity and mortality worldwide. Percutaneous transluminal coronary angioplasties (PTCA) is now a well established treatment for widening the lumen of coronary arteries stenosed by atherosclerotic lesions. The main limitation of PTCA is definitely restenosis in 30C40% of individuals, typically happening between 1C3 weeks [1], [2]. A number of medical and angiographic variables, including advanced age, diabetes mellitus, hyperlipidaemia, hypertension, unstable angina, severe coronary artery stenosis and long lesions, have been reported to be associated with an increased risk of restenosis after PTCA [3]C[6]. However, only 30% of restenosis could be predicted from medical and angiographic variables [5]. The hypothesis of a genetic susceptibility to explain the 30% to 40% of individuals affected by restenosis has been raised. Inappropriate activation of the reninCangiotensin system may play a part in the development of many cardiovascular disorders [7], [8]. Experimental studies favor the major role of the renin angiotensin system (RAS) in vessel healing after PTCA [9]C[11]. A common insertion/deletion polymorphism within the angiotensin-I transforming enzyme gene (ACE-I/D) has been reliably associated with considerable variations in the plasma and cells angiotensin-converting enzyme (ACE) activity inside a codominant fashion not only in individuals of Western descent, but also in additional populations such as Hispanics [12]C[14]. Individuals transporting the D allele have higher ACE activity, which has been proposed as an intermediate phenotype of potential relevance for the development of high blood pressure and subclinical atheroma (i.e., higher intima-media thickness of the carotid artery) [13], [15]. It has been suggested the incidence of coronary restenosis after a percutaneous coronary treatment is much higher in individuals with the angiotensin transforming enzyme DD genotype (which is definitely associated with particularly high plasma angiotensin transforming enzyme levels) than in others. However, these studies possess yielded apparently conflicting results. These disparate findings may be partly due to insufficient power, false-positive results, and publication biases. The interpretation of these studies has been further complicated by the use of different populations. We consequently Balapiravir (R1626) performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between ACE I/D polymorphisms and post-PTCA restenosis risk. Materials and Methods Literature Search Strategy Electronic databases (Pubmed, EMBASE, ISI Web of Technology, EBSCO, Cochrane Library databases and CNKI) were looked up to March 2013 for those genetic association studies evaluating the ACE-I/D polymorphism and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) in humans in all languages. The search strategy contained both medical subject heading terms and text terms as follows: angiotensin-converting enzyme or ACE or peptidyl-dipeptidase A, in combination with angioplasty or stent.Significant associations were found in restenosis risk after coronary stenting; while marginal significant associations were observed in restenosis risk after balloon PTCA. picture of the relationship between ACE I/D polymorphism and post-PTCA restenosis risk. Methods Databases including Pubmed, EMBASE, ISI Web of Technology, EBSCO, Cochrane Library databases and CNKI were looked to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, dealing with heterogeneity and publication bias. Results A total of 33 cohort studies including 11,099 subjects were included. Inside a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27C2.04; em P /em 10?5). In the subgroup analysis by intervention, significantly increased risks were also found in PTCA-stent and PTCA-balloon for the DD genotype of the polymorphism. Conclusions Our meta-analysis showed the DD genotype of ACE I/D polymorphism was significantly associated with improved risk of restenosis, particularly for PTCA-stent. Intro Coronary artery disease (CAD), including its most severe complication, myocardial infarction (MI), is the leading cause of morbidity and mortality worldwide. Percutaneous transluminal coronary angioplasties (PTCA) is now a well established treatment for widening the lumen of coronary arteries stenosed by atherosclerotic lesions. The main limitation of PTCA is definitely restenosis in 30C40% of individuals, typically happening between 1C3 weeks [1], [2]. A number of medical and angiographic variables, including advanced age, diabetes mellitus, hyperlipidaemia, hypertension, unstable angina, severe coronary artery stenosis and long lesions, have been reported to be associated with an increased risk of restenosis after PTCA [3]C[6]. However, only 30% of restenosis could be predicted from medical and angiographic variables [5]. The hypothesis of a genetic susceptibility to explain the 30% to 40% of individuals affected by restenosis has been raised. Inappropriate activation of the reninCangiotensin system may play a part in the development of many cardiovascular disorders [7], [8]. Experimental studies favor the major role of the renin angiotensin system (RAS) in vessel healing after PTCA [9]C[11]. A common insertion/deletion polymorphism within the angiotensin-I transforming enzyme gene (ACE-I/D) has been reliably associated with considerable variations in the plasma and cells angiotensin-converting enzyme (ACE) activity inside a codominant fashion FANCF not only in individuals of Western descent, but also in additional populations such as Hispanics [12]C[14]. Individuals transporting the D allele have higher ACE activity, which has been proposed as an intermediate phenotype of potential relevance for the development of high blood pressure and subclinical atheroma (i.e., higher intima-media thickness of the carotid artery) [13], [15]. It has been suggested the fact that occurrence of coronary restenosis after a percutaneous coronary involvement is a lot higher in sufferers using the angiotensin changing enzyme DD genotype (which is certainly associated with especially high plasma angiotensin changing enzyme amounts) than in others. Nevertheless, these studies have got yielded evidently conflicting outcomes. These disparate results may be partially due to inadequate power, false-positive outcomes, and publication biases. The interpretation of the studies continues to be further complicated through different populations. We as a result performed a meta-analysis from the released research to clarify this inconsistency also to establish a extensive picture of the partnership between ACE I/D polymorphisms and post-PTCA restenosis risk. Components and Methods Books Search Strategy Digital directories (Pubmed, EMBASE, ISI Internet of Research, EBSCO, Cochrane Library directories and CNKI) had been researched up to March 2013 for everyone hereditary association studies analyzing the ACE-I/D polymorphism and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) in human beings in Balapiravir (R1626) all dialects. The search technique included both medical subject matter heading conditions and text words and phrases the following: angiotensin-converting enzyme or ACE or peptidyl-dipeptidase A, in conjunction with angioplasty or stent or balloon or stenting or percutaneous or PTCA, and coupled with hereditary or polymorphism(s) or variants(s) or genotype or gene(s). Eligible Research and Data Removal Eligible studies acquired to meet every one of the pursuing requirements: (1) first papers containing indie data.