Angiotensin-converting Enzyme Gene Polymorphism Research Articles

Polycystic Ovary Syndrome is Affected and Protected by DD and DI Genotypes of Angiotensin Converting Enzyme, Respectively: An Update of a Meta-Analysis

Objectives: Angiotensin converting enzyme (ACE) is an important enzyme involved in the physiopathology of renal, cardiovascular and ovarian systems. One of these ACE related diseases is polycystic ovary syndrome (PCOS). Materials and Methods: We intend to update the only meta-analysis written by Jia et al in 2013 on the association of ACE gene polymorphism and risk of PCOS. The reason of our attempt to update this meta-analysis was that they found no significant relation in their meta-analysis. For this aim, we searched in databases for relevant documents. Results: We found 8 relevant papers, 6 of which had been covered by Jia et al meta-analysis. In order to perform this meta-analysis, we used comprehensive meta-analysis software. The analysis was done through P value and sample size of each study based on fixed-effect model. Analyses were performed in 5 different groups of alleles and genotypes. Among these 5 analyses, 4 of them were statistically significant. Hereby, we concluded that DD genotype of ACE is a risk factor for PCOS (P value = 0.013; odds ratio [OR] = 1.195), while DI is the protecting genotype (P = 0.009; OR = 0.819). Conclusion: Hence, it is suggested to use a very low dose of captopril as an ACE inhibitor in the PCOS patients having DD genotype in future as a clinical trial, just as a scientific model. Further investigation on ovary ACE system is needed. Keywords Author Keywords:Angiotensin converting enzyme inhibitors; Meta-analysis; Polycystic ovary syndrome KeyWords Plus:INSULIN-RESISTANCE; GENE POLYMORPHISM; PCOS; WOMEN; STIMULATION; ASSOCIATION; EXPRESSION; ESTRADIOL; SYSTEM; RISK

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients.

Whether the renin-angiotensin-aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly. The study included one hundred and seventeen acromegalic patients (62F/55M, age: 50.2 ± 12.3 years) and 106 healthy controls (92F/14M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype. The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16-60) vs. 12 (5-36)µg/L, p < 0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow Apeak values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms. Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects

Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case–control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively). The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD.

ACE serum level and I/D gene polymorphism in children with obstructive uropathies and other congenital anomalies of the kidney and urinary tract

The aim of this study was to investigate the association of an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) gene with serum ACE level in relation to the type and severity of malformations from congenital anomalies of the kidney and urinary tract (CAKUT) spectrum. A group of 134 Bulgarian children with CAKUT divided into four subgroups according to the leading malformation and 109 controls were genotyped by classical polymerase chain reaction. The quantitative determination of serum ACE was performed by ELISA method. A significant elevation of DD-genotype was observed in high-grade hydronephrosis compared to low-grade (43% vs. 9%). The carrying of DD-genotype was associated with higher risk for severe hydronephrosis with OR = 7.5 (95% CI: 1.242÷45.278; P = 0.028). Also, elevated serum ACE concentrations in patients with high-grade compared to low-grade hydronephrosis (237.4 ± 45 ng/mL vs 180.5 ± 64 ng/mL; P = 0.0065) were found. ACE level was significantly lower in patients with unilateral renal agenesis; hypo/dysplasia and multicystic dysplastic kidney (156.6 ± 54 ng/mL) than controls (200.6 ± 56.7 ng/mL; P = 0.005) and the remaining CAKUT subgroups. The DD genotype of I/D ACE polymorphism encodes the highest serum ACE level may be an additional genetic risk factor contributing to the severe hydronephrosis in Bulgarian patients with obstructive uropathies in contrast to other investigated categories of CAKUT malformations.

Association of ACE, VEGF and CCL2 gene polymorphisms with Henoch-Schönlein purpura and an evaluation of the possible interaction effects of these loci in HSP patients.

Henoch-Schönlein purpura (HSP) is a multisystem, small vessel, leucocytoclastic vasculitis. It is predominantly a childhood vasculitis, rarely reported in adults. Studies have shown that several different genetic factors such as genes involved in inflammatory system and renin-angiotensin system (RAS) are important in the pathogenesis of Henoch-Schönlein purpura. The purpose of this study was to evaluate the independent effect of 3 gene polymorphisms including CCL2-2518 C/T, VEGF-634G/C and ACE(I/D) with HSP disease and their possible joint interactions in developing the disease. In this case-control study 47 HSP cases and 74 unrelated healthy controls were enrolled for evaluation. All individuals were genotyped for CCL2-2518C/T, VEGF-634G/C and ACE(I/D) gene polymorphisms. The possible association of these polymorphisms with susceptibility to develop HSP disease independently and in different joint combinations was evaluated. The frequencies of TT genotype and T allele of CCL2-2518C/T gene polymorphism and CC genotype and C allele of VEGF-634G/C gene polymorphism were significantly high in HSP children (p-values = 0.005 and = 0.007 respectively). Interestingly, studying the joint interaction of these 2 genotypes (CC genotype of VEGF G-634C and TT genotype of CCL2 C-2518T) in this cohort showed a more significant effect in the development of the disease (p < 0.000, OR = 6.009). The frequency of TT genotype of CCL2 gene when combined with II genotype of ACE gene in HSP children was significantly higher (p < 0.000, OR = 4.213). The results of this pilot study provide evidence of the possible gene-gene interaction effects of CCL2, VEGF and ACE genes in developing HSP disease.

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study

BackgroundThe role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. MethodsThis single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. ResultsThe II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI=0.114–0.558; p=0.007), for that of II genotype was 1.93 (95% CI=0.86–4.3; p=0.107) and for DD genotype was 7.225 (95% CI; 1.88–27.6; p=0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds=4.25; 95% CI=2.01–6.7; p=0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. ConclusionACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.

Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population.

The link between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the prevalence of type 2 diabetes mellitus (T2DM) developing in the Saudi Arabian population remains controversial. The aim of the present study was to evaluate the association between the ACE I/D gene polymorphism and the risk of developing T2DM and hypertension (HTN) in Saudi Arabian individuals. A total of 220 individuals consisting of 48 control subjects, 70 T2DM, 48 HTN, and 54 T2DM with HTN patients were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of the DD genotypes was conducted with an insertion-specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene was 6.8, 42.6 and 48.6% in T2DM patients, 4.2, 50 and 45.8% in HTN patients, 5.6, 55.5 and 38.9% in T2DM patients with HTN and 58.3, 37.5 and 4.2% in control subjects, respectively. The frequency for the D allele was 70% in T2DM patients, 70.8% in HTN patients and 66.7% in T2DM patients with HTN as compared with 22.9% in the control subjects. The genotype and allele frequency of the ACE gene polymorphism varied significantly (P<0.05) in the patients when compared with the control subjects. The current study demonstrated that the ID/DD genotype and the D allele of the ACE gene I/D polymorphism were strongly associated with the risk of T2DM and HTN developing in a Saudi Arabian population.

Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome, Effect on Biopsy Findings

ABSTRACTObjective: Angiotensin converting enzyme (ACE) converts angiotensin I into angiotensin II. The ACE gene shows an I/D polymorphism, which correlates with ACE concentrations. The aim of this study is to evaluate the distribution of the ACE I/D genotype in children with idiopathic nephrotic syndrome (INS) and healthy controls and study the effect of this polymorphism on clinical and pathologic findings. Methods: ACE gene I/D polymorphism of 104 patients with INS and 119 controls were determined. Results: The DD, ID, and II genotypes were found in 58.7%, 22.1%, and 19.2% of the patients, and in 79.8%, 2.5%, and 17.6% of controls, respectively (p > 0.05). The ID genotype was seen more frequently in patients resistant to treatment. Conclusion: The observed differences with previous reports suggest the influence of the genetic background on disease course. The ACE I/D gene polymorphism's role seems to be more important in renal disease progression than susceptibility.

Research progress of angiotensin converting enzyme gene polymorphism and kidney disease in children

Angiotensin converting enzyme (ACE) gene is one of the major candidate genes for genetic susceptibility to kidney disease, but there is still a controversy on the correlation between ACE gene polymorphism and kidney disease.In this paper, the research on the correlation between ACE gene polymorphism and kidney disease in children is reviewed. Key words: Angiotensin converting enzyme; Gene polymorphism; Children; Kidney disease

Correlation between polymorphism of angiotensin-converting enzyme gene and the lower extremity atherosclerosis in type 2 diabetes mellitus patients

Objective: To explore the correlation between polymorphism of the angiotensin-converting enzyme (ACE) gene and lower extremity atherosclerosis (LEA) in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 380 patients diagnosed with T2DM in Department of Endocrinology from June 2015 to March 2016 were enrolled and divided into two groups: group A had no LEA (n=120) and group B had LEA(n=260). Color doppler ultrasound was used to detect the vascular lesions of the patients. For all patients in groups A and B, the polymerase chain reaction (PCR) was applied to determined the insertion/deletion polymorphism in intron 16 of the ACE gene of the patients. Then the blood pressure, blood lipid, glycated hemoglobin, and renal function were measured. Furthermore, the measured data was compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for LEA. Results: There was no significant statistical difference in age, sex, smoking and disease course between the two groups. The frequencies of DD genotype and D allele in the ACE gene of group B were much higher than those in group A. More specifically, DD genotype frequency was 18.8% in group B and 9.2% in group A, D allele frequency was 36.8% in group B and 29.2% in group A (all P<0.05). Multivariate logistic regression analysis showed that DD genotype in ACE gene (OR=2.744, 95% CI: 1.326-5.682), systolic blood pressure (OR=1.725, 95% CI: 1.072-2.778), total cholesterol (OR=3.785, 95% CI: 1.796-7.978), and glycated hemoglobin (OR=2.612, 95% CI: 1.602-4.258) were risk factors for LEA in T2DM patients. Conclusions: ACE gene insertion/deletion polymorphism was associated with the incidence of LEA in T2DM patients. DD genotype of the ACE gene may be a genetic risk factor for T2DM patients with concurrent atherosclerosis.

The relationship between hormones level and body mass index with insertion and deletion (D/I) polymorphism of ACE gene in infertile patients with polycystic ovary syndrome

The relationship between hormones level and body mass index with insertion and deletion (D/I) polymorphism of ACE gene in infertile patients with polycystic ovary syndrome

Higher Plasma Glucose Level In Hypertensive Patient With Angiotensin Converting Enzyme Gene Deletion Of Intron 16

Background Renin Angiotensin Aldosteron System plays major role in hypertension pathophysiology. Has been proposed that half of individuals with essential hypertension are considered insulin resistant. Angiotensin Converting Enzyme gene polymorphism taking the control of ACE level in human plasma. There might be a correlation between ACE gene polymorphism and plasma glucose level.Objective This study sought to investigate ACE gene polymorphism insertion/deletion in hypertensive patients and its correlation with plasma glucose level.Method A total of 100 hypertensive patients at Saiful Anwar cardiovascular outpatients clinic who received ACEi at least 8 weeks were included. ACE genotype were determined by polymerase chain reaction method, and plasma glucose level was measured by enzymatic colorimetric assay method.Result The II, ID, and DD genotype were observed in 48%, 29% and 23% of participant, respectively. The fasting and 2 hours post prandial plasma glucose were significantly higher in DD genotype patients. The insertion/deletion polymorphisms were not related significantly to age, sex, cough, and controlled blood pressure of those patients.Conclusion This study showed that 23% of hypertensive patients had DD genotype with higher plasma glucose level as compare to those of II and ID genotype.

Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia.

Objective:To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage.Methods:Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121.Results:Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior.Conclusion:Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Association of AGTR1 and ACE2 gene polymorphisms with structural atrial fibrillation in a Chinese Han population.

The renin-angiotensin system (RAS) is thought to play an important role in atrial fibrillation (AF). The RAS contains the ACE/AngII/AGTR1 axis and the ACE2/Ang(1-7)/MAS axis, which restrict each other via mutual antagonism and regulate myocardial hypertrophy, fibrosis and remodelling. The aim of our study was to investigate the association between single nucleotide polymorphisms (SNPs) in angiotensin-II type-1 receptor (AGTR1) and angiotensin-converting enzyme 2 (ACE2) and structural AF in a Chinese Han population. The SNPs (rs1492100, rs1492099, rs1492097, rs3772616) in AGTR1 and the SNP rs6632677 in ACE2 were compared in 300 structural AF patients (67.61±12.56 years) and 300 controls (66.08±12.47 years). The genotype frequencies of SNP rs1492099 in AGTR1 in the structural AF cohort vs controls were as follows: GG, 72.7 vs 83.0%; AG 26.0 vs 16.3%; AA 1.3 vs 0.7% (P=0.009). The frequency of the minor allele of SNP rs1492099 in AGTR1 was 14.2% in the structural AF group compared with 8.8% in the controls (t=0.004; odds ratio [OR], 1.727; 95% confidence interval [CI]: 1.154-2.487). In addition, the genotype frequencies of SNP rs6632677 in ACE2 in the structural AF male patients vs male controls were as follows: GG, 70.5 vs 83.1%; CG 26.3 vs 15.6%; and CC 3.2 vs 1.3% (P=0.029). The frequency of the minor allele of SNP rs6632677 in ACE2 was 16.3% in structural AF male patients compared with 9.1% in male controls (P=0.008; OR, 1.954; 95%CI: 1.196-3.192). Furthermore, we found an interaction between the SNP rs6632677 in ACE2 and the SNPs (rs1492100/rs1492099/rs3772616) in AGTR1 in structural AF patients by the multifactor dimensionality reduction (MDR) method. The results indicate that polymorphism rs1492099 in the AGTR1 gene is associated with structural AF in a Chinese Han population. It was hypothesized that the ACE2 gene, which maps to the X chromosome, may be correlated with the risk of structural AF in a Chinese Han male population. Furthermore, we found an interaction between ACE2 and AGTR1 in structural AF patients in a Chinese Han population.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

Association of Angiotensin-Converting Enzyme Gene Polymorphisms and Nephropathy in Diabetic Patients at a Tertiary Care Centre in South India.

Background:Genetic polymorphisms of the angiotensin-renin pathway have been thought to influence the development of diabetic nephropathy. However, there are conflicting results regarding this association in previous studies on populations with varying ethnicity.Aims:Primary aim was to compare the frequency of distribution of angiotensin-converting enzyme (ACE) gene (insertion/deletion [I/D]) polymorphism in Tamilian Indian type 2 diabetic individuals with and without microalbuminuria. Secondary objective was to compare the frequency of distribution of the 3 genotypes in diabetic patients with urinary albumin/creatinine ratio (ACR) < 30 mg/dL, urinary ACR = 30 to 300 mg/dL, and urinary ACR > 300 mg/dL.Methods:A total of 179 consecutive diabetic individuals between 40 and 70 years, from Puducherry and Tamilnadu of Dravidian descent participated in the study conducted from 2012 to 2014. Inclusion criteria were as follows: age ≥ 40 years and duration of type 2 diabetes mellitus for ≥5 years. Patients were divided into 2 groups based on ACR values. Group 1 consisted of 50 individuals with urinary ACR < 30 mg/g of creatinine, and group 2 consisted of 129 individuals with urinary ACR > 30 mg/g. Angiotensin I–converting enzyme (ACE) gene polymorphism was determined by allele-specific polymerase chain reaction method using a primer pair flanking the polymorphic region of its intron 16. Furthermore, group 2 patients were subdivided into those with urinary ACR = 30 to 300 mg/g of creatinine and those with urinary ACR > 300 mg/g of creatinine, and distribution of ACE gene polymorphism was compared in the three groups.Statistics:Statistical analysis was done using SPSS version 17.0. Independent Student t test was used to compare mean values between the 2 groups. Odds ratio was calculated for testing association between ACE gene (I/D) polymorphism and presence of microalbuminuria. P < .05 was considered significant. Comparison of ACE genotypes among 3 groups of patients (ACR < 30 mg/g, ACR = 30-300 mg/g, and ACR > 300 mg/g) was done using 1-way analysis of variance with Bonferroni multiple comparison test as post hoc analysis.Conclusions:Heterozygous I/D genotype was more frequent in the study population (45.8%) than the other genotypes. There was no difference in the genotype distribution in patients with varying levels of albuminuria.

Association between angiotensin converting enzyme gene polymorphism and hypertension with abnormal savda in Uyghur people

Association between angiotensin converting enzyme gene polymorphism and hypertension with abnormal savda in Uyghur people

A New Investigative Approach: How the Angiotensin-Converting Enzyme Gene Interacts with Coronary Risk Factors

How each Angiotensin-Converting Enzyme (ACE) genotype modulates the magnitude of the effect of each coronary risk factor. Background: Coronary Artery Disease (CAD) is based on atherosclerosis, which is a multifactorial-multigenic disease. This study investigated when interacting with them in the genesis of this pathology. Methods: The study included 630 subjects, including one group with 396 CAD-confirmed patients and another with 234 controls without angiographic lesions. Classical risk factors of CAD and ACE gene polymorphisms were evaluated using nested PCR. The association between the DD, ID and II genotypes with classical risk factors was analysed statistically by comparing the patient and control groups using the binomial frequency comparison test and the power test. Results: Of the 630 individuals, 286 presented the DD genotype, and there were 251 ID genotypes and 93 II genotypes. In the comparative analysis of the genotype frequencies between the patient and control groups, the DD genotype showed the most significant difference and the highest power (p=0.0020; power=0.8454). In the analysis of the interaction between risk factors and the ACE genotype in the DD genotype, a significant difference and a high power in the family history of CAD (p=0.0043; power=0.08355); (p=0.0010; power=0.9155), high total cholesterol levels (p<0.0001; power=0.9983) and high LDL cholesterol levels (p=0.0004; power=0.9702) were found. Conclusion: The results indicate that ACE genotypes interact differently with the same risk factors in each individual, influencing the development of CAD.

Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting.

Background and objective:Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting.Methods and results:Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years.Conclusion:Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

Predisposition of Angiotensin-converting Enzyme Deletion/Deletion Genotype to Coronary Artery Disease with Type 2 Diabetes Mellitus in South India.

Background:Worldwide, South Asians contribute to a high proportion of coronary artery disease (CAD) burden, mainly attributed to a high prevalence of diabetes. Early identification of such high-risk individuals would enable aggressive disease modification and prevention of complications. Definition of susceptible genotypes early in the course of disease may be one such avenue for reduction in morbidity and mortality from CAD.Aim:Our study was aimed to investigate the insertion/deletion polymorphism of angiotensin-converting enzyme (ACE I/D) gene and susceptibility to CAD in patients with type 2 diabetes mellitus (T2DM) in a South Indian population.Subjects and Methods:ACE (I/D) genotyping was performed by polymerase chain reaction specific primer for 187 CAD patients and 185 age- and sex-matched controls.Results:We observed that the ACE“II” genotype was found to be significantly associated with CAD patients (odds ratio [OR] = 1.689; P = 0.028). However, multiple logistic regression analysis revealed that ACE “DD” genotype was found to be most predominant risk factor for CAD patients with T2DM (OR = 6.118; P = 0.001).Conclusion:Our results showed that ACE (I/D) genotypes and alleles presented functional dimorphism in the development of CAD and CAD with T2DM patients in South India. This finding may be extremely useful in identifying subsets of patients where early aggressive treatment of risk factors is warranted.