I/D polymorphism of the ace gene as a marker of different cardiovascular diseases. relations with hypertension, coronary atherosclerosis and restenosis after coronary stent implantion (original) (raw)
Related papers
Atherosclerosis, 2014
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing instent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR = 1.31, 95% CI: 1.04-1.66, P = 0.018) and decreased frequencies of GAGATG (OR = 0.47, 95% CI: 0.25-0.88, P = 0.011) and AGAGCA (OR = 0.15, 95% CI: 0.02-0.65, P = 0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Clinical Science, 2004
The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95 %). Restenosis rates among genotypes were 31.2 % DD, 25.5 % ID and 28.8 % II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7 + − 18.6 units/l compared with 22.8 + − 12.8 units/l; P = 0.0001) and a strong independent predictor of ISR [OR (odds ratio) = 3.70; 95 % CI (confidence interval), 2.40-5.71; P < 0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR = 0.16; 95 % CI, 0.04-0.69; P = 0.014; and patients with AMI, OR = 0.21; 95 % CI, 0.061-0.749; P = 0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7 % DD, 24.3 % ID and 17.6 % II (P = 0.02; DD compared with non-DD OR = 1.57; 95 % CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.
Experimental and Molecular Pathology, 2014
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing instent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR = 1.31, 95% CI: 1.04-1.66, P = 0.018) and decreased frequencies of GAGATG (OR = 0.47, 95% CI: 0.25-0.88, P = 0.011) and AGAGCA (OR = 0.15, 95% CI: 0.02-0.65, P = 0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Circulation, 1998
Background-Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion (I/D) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. Methods and Results-One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels ϮSEM) were 40.8Ϯ3.5 and 20.7Ϯ1.0 U/L, respectively (PϽ.0001). Diameter stenosis percentage and minimum luminal diameter at 6 months showed statistically significant correlation with plasma ACE level (rϭ.352 and Ϫ.387, respectively PϽ.001). Twenty-one of 62 patients (33.9%) with D/D genotype, 13 of 80 (16.3%) with I/D genotype, and 1 of 34 (2.9%) with I/I genotype showed recurrence; the restenosis rate for each genotype is consistent with a codominant expression of the allele D. Conclusions-In a selected cohort of patients, both the D/D genotype of the ACE gene, and high plasma activity of the enzyme are significantly associated with in-stent restenosis. Continued study with clinically different subsets of patients and various stent designs is warranted. (Circulation. 1998;97:147-154.)
2008
"BACKGROUND: It has been suggested that the incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with a 287-bp alu repeat sequence within intron 16 of the angiotensin-I-converting enzyme (ACE) gene (deletion allele) than in others, but published studies are conflicting. METHODS: The presence (insertion) or absence (deletion) of a 287-bp alu repeat sequence within intron 16 of the ACE gene (I/D polymorphism) was analyzed by polymerase chain reaction in a group of 168 patients with coronary artery disease who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. RESULTS: Distribution of angiotensin converting enzyme I/D polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made considering the type of stent implanted. On the other hand, the whole group of coronary artery disease patients showed increased frequencies of the D allele (p=0.00001, OR=2.17, 95% CI=1.49-3.16) and ID genotype (p=0.0002, OR=2.58, 95%CI=1.49-4.47) when compared to healthy controls. CONCLUSIONS: Genetic variations of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican mixed racial ancestry individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting."
Plasma Activity and Insertion/Deletion Polymorphism of Angiotensin I–Converting Enzyme
Circulation, 1998
Background —Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion ( I/D ) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. Methods and Results —One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels (±SEM) were 40.8±3.5 and 20.7±1....
Effects of ACE polymorphisms and other risk factors on the severity of coronary artery disease
Genetics and Molecular Research, 2013
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 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (4): 6895-6906 (2013) A.I. Guney et al. 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.
Genetics and Molecular Research, 2015
ACE levels (P < 0.001). The highest ACE levels were found in those with the DD genotype. Other genotypes also presented statistically significant differences. We observed a significant difference between the control and coronary patient groups regarding the levels of total cholesterol, triglyceride, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol (P < 0.05). ACE (I/D) genotypes and serum ACE levels may be associated with risk factors and the development of CAD.