Angiotensinogen Polymorphisms Research Articles

Renin-Angiotensin System Genes Polymorphisms in Patients With COVID-19 and Its Relation to Severe Cases of SARS-CoV-2 Infection.

Different variants of single nucleotide polymorphisms (SNPs) of angiotensinogen (AGT), angiotensin-converting enzyme type 1 (ACE1), and angiotensin II receptors type 1 (AGTR1) and 2 (AGTR2) genes determine different susceptibility to cardiovascular disease (CVD) and hypertension, which can be considered as risk factors for fatal outcomes among coronavirus disease 2019 (COVID-19) patients. The objective of our study was to assess the relation between the frequency of SNPs of the renin-angiotensin system (RAS) components, and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The cross-sectional study included 100 patients with a laboratory-confirmed diagnosis of COVID-19 admitted to the hospital. Criteria for severe COVID-19 included respiratory rate (RR) > 30/min, blood oxygen saturation (SpO2) ≤ 93%, signs of unstable hemodynamics with systolic blood pressure (SBP) < 90 and/or diastolic blood pressure (DBP) < 60 mm Hg. All patients were identified with alleles and genotypes of the polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene using the polymerase chain reaction method in human DNA preparations on real-time CFX96C1000 Touch, Bio-Rad equipment (Syntol, Russia). Statistical analysis was performed in R v.4.2. Patients were divided into groups with severe (n = 44) and moderate COVID-19 (n = 56). For ACE1 rs1799752, a significant deviation from the population distribution was detected in both studied subgroups. A higher frequency of the C allele SNP rs5186 AGTR1 gene was detected in the group with severe disease. More frequent A/A genotype of SNP rs1403543 AGTR2 was detected among females with severe COVID-19. Haplotype analysis revealed more common DCG haplotype among patients with severe COVID-19. The odds ratio for severe COVID-19 in the presence of the DCG haplotype was 3.996 (95% confidential interval: 1.080 -14.791, P < 0.05). Our data suggest that the SNP genes of the RAS components, may allow to identify groups of patients predisposed to a more severe course of COVID-19.

Association of rs5051 and rs699 polymorphisms in angiotensinogen with coronary artery disease in Iranian population: A case-control study.

Coronary artery disease (CAD) is the third most common cause of mortality globally (with 17.8 million deaths annually). Angiotensinogen (AGT) and polymorphisms in this gene can be considered as susceptibility factors for CAD. We performed a retrospective case-control study to determine the correlation of AGT rs5051 and rs699 polymorphisms with CAD in an Iranian population. We genotyped 310 CAD patients and 310 healthy subjects using polymerase chain reaction-based methods. To confirm the accuracy of the screening approach, 10% of genotyped subjects were validated using gold-standard Sanger Sequencing. To evaluate the effect of the candidate polymorphisms, white blood cells were randomly purified from the subjects and AGT expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Sex stratification indicated a significant correlation between CAD and male sex (P = .0101). We found a significant association between the rs5051 A allele (P = .002) and the rs699 C allele, and CAD (P = .0122) in recessive and dominant models. Moreover, our findings showed a significant association of the haplotype, including the rs5051 A/A and rs699 T/C genotypes, with CAD (P = .0405). Finally, AGT mRNA levels were significantly decreased in patients harboring the candidate polymorphisms (P = .03). According to our findings The AGT rs5051 A and AGT rs699 C alleles are predisposing variants of CAD risk and severity in the Iranian population.

Angiotensinogen: in-silico insight to mutations, protein-protein interactions and evolution

In this era of rapidly evolving genetic and non-genetic diseases, in-silico analysis of disease related proteins has proven beneficial in identification and characterization of potential therapeutic targets. In present study, angiotensinogen (AGT) was studied for its sequence based ortholog and paralogs, structural characterization, mutational analysis, protein interactions and evolutionary changes. Sequence studies identified 194 orthologs and 36 paralogs of AGT. Functional analysis AGT polymorphisms revealed the association of M235T with increased AGT stability. Protein-protein interaction analysis exposed the involvement of AGT in metabolic diseases. So, this study provided base for the experimentally proven association of M235T polymorphism with metabolic diseases. Moreover, it presents AGT as strong therapeutic target for the control of these diseases.

Effects of AGT and AGTR1 Genetic Polymorphisms and Changes in Blood Pressure Over a Five-Year Follow-Up.

The renin-angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1) may increase susceptibility to elevated BP and hypertension. This study investigated the effects of AGT rs699 and AGTR1 rs5186 single nucleotide polymorphisms (SNPs) on BP at baseline and at a 5-year follow-up. The study population consisted of participants from the Electricity Generating Authority of Thailand cohort study (n=354); data were collected at baseline (2013) and 5 years later (2018). Genotyping of the two SNPs was performed using TaqMan® assay and statistical analyses were performed with SNPStats software. The frequencies of the two SNPs were within the Hardy-Weinberg equilibrium (p=0.22 for AGT rs699 and p=0.06 for AGTR1 rs5186). For each SNP, mutant genotypes were significantly associated with increased systolic BP and/or diastolic BP in the codominant and recessive models. Risk alleles of AGT rs699 and AGTR1 rs5186 were associated with increased odds of hypertension and hypertension with metabolic syndrome at follow-up. Overall, our results suggest that polymorphisms of genes in the renin-angiotensin system increase susceptibility to the development and progression of hypertension and the development of the metabolic syndrome.

Association of the ACE and AGT gene polymorphisms with global disparities in COVID-19-related deaths.

The aim of the study was to investigate the gene polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin type 1 receptor (AT1R) in association with coronavirus disease 2019 (COVID-19) mortality rates worldwide. The prevalence of ACE I/D, AGT M235T, and AT1R A1166C alleles' frequencies in different populations was assessed. Data on COVID-19-related cases and deaths were acquired from the European Center for Disease Prevention and Control, which included weekly reports by country and continent. An Excel tool was developed to visualize the acquired data of mortality and incidence by classifying them by continent/country across specific periods of time. Spearman's nonparametric correlation was used to evaluate the association between country-based frequencies in RAS gene polymorphisms and COVID-19-related deaths. While China constituted the initial reservoir of COVID-19, incidence/mortality rates in Europe and America outnumbered the figures in the former. A clear association was identified between death rates and ACE D/I ( r = 0.3659; P = 0.033), as well as AGT A/G variants ( r = 0.7576; P = 0.015). Data on AT1R polymorphisms suggested no correlation with mortality rates. Our results demonstrated a significant disparity in COVID-19-related susceptibility and mortality among different populations and corroborate the importance of gene polymorphisms in predicting and consequently improving patients' outcomes.

Genetic Polymorphism in Angiotensinogen and Its Association with Cardiometabolic Diseases.

Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases.

The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients.

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.

Prize‐winning abstracts from BSACI/WAO 2022 meeting

Prize‐winning abstracts from <scp>BSACI</scp>/<scp>WAO</scp> 2022 meeting

The Association of Angiotensin-converting Enzyme I/D and Angiotensinogen M235T Polymorphism Genes with Essential Hypertension: A Meta-analysis

Objective: Essential or primary hypertension in developing countries has become a major problem. Recent hypertension-related research has revealed susceptibility genes in genome-wide association studies. Several studies have associated angiotensin converting enzyme (ACE) I/D and angiotensinogen (AGT) M235T polymorphisms with essential hypertension, but results have been inconsistent. This meta-analysis aimed to clarify the association of AGT and ACE polymorphisms with the risk of primary hypertension.&#x0D; Methods: PubMed, Embase database, Medline, Goggle Scholar, Scopus.com, as well portal Garuda (www.garuda.ristekdikti.go.id) and Cochrane were used to retrieve all publications from 2006-2020 relating risk factors for hypertension with ACE I/D and AGT M235T polymorphisms. The meta-analysis was conducted from January –April 2020. All association studies were identified and data extracted from each study. Revman 5.3 software was used for meta-analysis to estimate odds ratios (OR) after extracting data and evaluating the quality of the enrolled studies.&#x0D; Results: A total of 27 studies (totaling 5,105 patients and 5196 controls) were identified. The overall effect suggested ACE I/D was significantly associated with primary hypertension (OR: 95%CI=1.51[1.29-1.77], p=0.004). There was no association between AGT M235T with risk of essential hypertension.&#x0D; Conclusion: This meta-analysis found significant association between ACE I/D gene polymorphisms with primary hypertension susceptibility. However, the AGT M235T gene had no association with the risk of primary hypertension. The Adrenoreceptor-beta/Renin Angiotensin System (ADRB/RAS) A allele should be considered a risk factor for essential hypertension.

Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson\u2019s disease

BackgroundRenin-angiotensin system (RAS) influences the central nervous system not only through its peripheral impact—the brain possesses its own local RAS. Studies showed altered RAS components in Parkinson’s disease (PD) and their association with oxidative stress which may be linked to neurodegeneration and dementia. Moreover, the protective functions of RAS blockade antagonists against cognitive decline and dementia have been suggested. This study aimed to examine whether genetic variability in RAS genes correlates with cognitive decline in PD.Methods and resultsWe genotyped single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT: rs699, rs4762), angiotensin II receptors (AGTR1: rs5186 and AGTR2: rs5194, rs1403543) genes, as well as insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE I/D) gene in 256 PD patients, divided into three groups: without cognitive decline, with mild cognitive impairment and with PD dementia. We did not find any significant differences in the frequencies of the analysed polymorphisms in any of the groups.ConclusionsDespite no direct correlation between the investigated polymorphisms in RAS genes and cognitive decline in PD, we believe the impact of those genotypes may be indirect, affecting RAS blockade treatment.

Handgrip Strength is more associated with blood glucose than ACE and AGT polymorphisms in hemodialysus patients

Background: Patients with chronic kidney disease (CKD) often present with comorbidities like hypertension and diabetes. These conditions are often associated with loss of strength, which is a strong predictor of mortality. In this sense, it is reasonable to investigate genetic and physiological markers that could be related to strength and identify variables associated with this phenomenon. Objective: This study aimed to investigate the influence of angiotensin-1 converting enzyme (ACE) and angiotensinogen (AGT) M235T polymorphisms, and blood glucose on handgrip strength (HGS) for CKD patients with and without diabetes mellitus (DM). Methods: Male patients (n = 84) participated in this cross-sectional study. Patients were grouped based on the diagnosis of DM or not. We evaluated HGS using a dynamometer and ACE and AGT polymorphism by polymerase chain reaction. Results: There were differences in HGS between groups. Follow up analyses indicated a difference in the distribution of ACE polymorphism alleles was associated with the reduction in HGS in the DM group. The same response was present for AGT. A negative correlation existed between blood glucose levels and HGS (r = -0.334 with p &lt; 0.05). Discussion: The present data suggests that there is a relationship between physical capacity and poor glycemic control. Conclusion: Our study demonstrated that blood glucose levels are associated with HGS in patients with CKD independent of ACE I/D and AGT M235T polymorphisms. Presence of DM may influence functional strength retention.

Key genetic variants in the renin-angiotensin system and left ventricular mass in a cohort of Polish patients with heart failure.

Heart failure (HF) is a complex disease that is under the control of different physiological systems. Left ventricular mass (LVM) is a strong predictor of HF. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF and LVM. The aim of this study is to examine the association between RAS genetic variants and HF and LVM in the cohort of Polish patients with HF. The study included 401 patients with HF. Two-dimensional M-mode echocardiography was used to assess LVM. Genomic DNA was extracted from blood, and genotyping of the angiotensin-converting enzyme (ACE) (rs4646994), angiotensinogen (AGT) (rs5051), and angiotensin II receptor type 1 (AGTR1) (rs5186) polymorphisms was carried out using polymerase chain reaction (PCR). A significant association was found between HF and the genotypes of G(-6)A AGT, and the homozygotes AA of AGT were significantly less common in the HF vs control group. The results of this study did not confirm the relationship between AGT, ACE and AT1R genetic variants with LVM in Polish patients with HF. Our results suggested that AGT polymorphism may play a protective role in the development of HF.

Risk Assessment Using the Association Between Renin-Angiotensin Genes Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called polymorphism and if it is less than 1%, then it is called a mutation.According to our findings, after thorough searching, which support the association of RAS genes polymorphisms with premature CAD, hypertension, hypertrophic cardiomyopathy, and atherosclerosis, we recommend additional studies in the form of clinical trials and meta-analyses aiming to create a specific diagnostic tool for CAD risk assessment and discovering the high-risk people as early as possible. Targeted gene therapy, being the future of medicine, needs to be taken into researchers' consideration. It can have promising results in these cases.

Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population.

Objective:This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population.Methods:We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism.Results:ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: –1.45 and −2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol.Conclusion:These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

Associations Between Polymorphisms of Endothelial Nitric Oxide Synthase, Matrix Metalloproteinase 3, Angiotensinogen, and Angiotensin II Type 1 Receptor and Risk of Restenosis After Percutaneous Coronary Intervention: A Meta-analysis

PurposePrevious studies have reported controversial results regarding the risk of restenosis with polymorphisms of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase 3 (MMP-3), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) after percutaneous coronary intervention (PCI). This study aimed to summarize the association between these polymorphisms and risk of restenosis after PCI. MethodsWe searched the electronic databases of PubMed, Embase, Cochrane's Library, and ClinicalTrials.gov for studies on the association of eNOS, MMP-3, AGT, and AT1R polymorphisms with restenosis. FindingsA total of 17 studies (7781 patients) were analyzed, including 5 studies on eNOS G298A (n = 912), 5 studies on MMP3 5A/6A (n = 4519), 6 studies on AGT M235T (n = 1801), and 7 studies on AT1R A1166C (n = 2477). For the G298A variant of the eNOS gene, the allele odds ratio (OR) was 1.685 (95% CI, 1.269–2.338; P < 0.001), the heterozygote OR was 2.144 (95% CI, 1.490–3.085; P < 0.001), the dominant OR was 2.078 (95% CI, 1.462–2.954; P < 0.001), and the overdominant OR was 0.496 (95% CI, 0.348–0.706; P < 0.001). For the 5A/6A variant of the MMP3 gene, the heterozygote OR was 0.839 (95% CI, 0.722–0.975; P = 0.022), the dominant OR was 0.846 (95% CI, 0.733–0.976; P = 0.022), and the overdominant OR was 1.141 (95% CI, 1.001–1.301; P = 0.049). For the M235T variant of the AGT gene, the heterozygote OR was 1.594 (95% CI, 1.179–2.155; P = 0.002), the dominant OR was 1.437 (95% CI, 1.077–1.918; P = 0.014), and the overdominant OR was 0.694 (95% CI, 0.555–0.869; P = 0.001). Positive results were observed in the AT1R gene A1166C polymorphism under 3 models (homozygote OR = 2.009; 95% CI, 1.433–2.816; P < 0.001; recessive OR 1.874; 95% CI, 1.353–2.595; P < 0.001; and dominant OR = 1.350; 95% CI, 1.105–1.649; P = 0.003). ImplicationsThe G298A variant of eNOS, the 5A/6A variant of MMP3, the M235T variant of AGT, and the A1166C variant of A1TR may increase the risk of restenosis after PCI.

Computational analyses prioritize and reveal the deleterious nsSNPs in human angiotensinogen gene

Angiotensinogen (AGT) is a key component of renin-angiotensin-aldosterone system (RAAS), which plays central role in blood pressure homeostasis. Association of AGT polymorphisms have been investigated in different ethnic populations in variety of cardiovascular and non-cardiovascular conditions. In this study, 354 non-synonymous SNPs (nsSNPs) of AGT were evaluated to predict damaging and structurally important variants. Majority of the deleterious nsSNPs occurred in the evolutionary conserved regions. Several of these nsSNPs were found to affect post-translational modifications like methylation, glycosylation, phosphorylation, ubiquitination etc. Structural evaluations predicted 19 variants as destabilizing and some of them were also predicted to destabilize the renin-AGT interaction. Therefore, the present computational investigation predicted pathogenic and functionally important variants of human AGT gene. The study has also shown that AGT deregulation is associated with survival outcome in patients with gastric and breast cancer, using microarray gene expression profile. Furthermore, the computationally screened nsSNPs can be analyzed in population based genotyping studies and may help futuristic drug development in the area of AGT pharmacogenomics.

Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population.

The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Association study of M235T and A-6G polymorphisms in angiotensinogen gene with risk of developing preeclampsia in Iranian population.

Preeclampsia (PE) is a life-threatening complication of pregnancy that accounts for 12% of all maternal deaths worldwide. The aim of this study is to investigate the relationships between the polymorphisms of angiotensinogen (AGT) gene and preeclampsia. In this study, 240 unrelated preeclampsia patients and 178 normotensive women were examined. Genomic DNA was extracted then we assessed M235T(C/T) and A-6G polymorphisms of the AGT gene. Genotyping of M235T and A-6G polymorphisms were performed using SSP-PCR and MS-PCR, respectively. A significant protective association was observed between A-6G G allele, A-6G A/G heterozygote genotype (OR=0.6, p=0.007 and OR=0.6, p=0.04) against PE. Furthermore, it was shown that two copies of A-6G A allele would increase PE risk (OR: 0.62, p=0.04). Our results did not show a significant association for M235T polymorphism and PE. However, the combinations of A-6G A/A genotype and M235T T/C genotype (OR=0.4, p=0.02) and also A-6G A/G genotype and M235T T/C genotype (OR=0.5, p=0.04) in controls represented a significant protective association against PE. According to the existence of significant correlation between two candidate polymorphisms, A-6G and M235T polymorphisms, with PE disease in our study, they may be considered as valuable factors in susceptibility to PE disease in Iranian women.

The relationship among angiotensinogen genes polymorphisms and hs-CRP and coronary artery disease.

ObjectiveTo assess the association of gene polymorphisms of angiotensinogen (AGT), the key factor in rennin‐angiotensin‐aldosterone system (RAAS), with high‐sensitivity C‐reactive protein (hs‐CRP) and coronary artery disease (CAD).MethodsThe current study recruited the patients who were hospitalized and assessed by coronary angiography for suspected CAD. The patients with documented CAD served as CAD group (n = 492) while the patients without documented CAD (n = 87) served as control group. We compared laboratory data and CAD risk factors between the two groups. Furthermore, we analyzed the association of AGT M235T, G217A, G152A, G‐6A, A‐20C genotypes with coronary artery stenosis and in‐stent restenosis.ResultsThere were significantly differences between two patient groups in sex, smoking history, diabetes mellitus, carotid atherosclerosis, lower limb arteriosclerosis, hs‐CRP, blood glucose, and the level of high‐density lipoprotein (HDL; P < 0.05). In CAD group, hs‐CRP levels increased with increasing number of coronary artery branches (1, 2, or ≥3; P < 0.01), and Gensini integral was positively correlated with hs‐CRP levels (r = 0.361, P < 0.01). Frequencies of genotype and allele distribution in individual angiotensinogen loci (M235T, G217A, G152A, G‐6A, A‐20C) did not differ in two patient groups. Following stratification of patients according to hs‐CRP levels (<1 mg/L, 1‐3 mg/L, and >3 mg/L), the distribution frequency of allele M235T was statistically different among the groups (P < 0.05).ConclusionIn CAD patients, M235T among several AGT gene polymorphisms is associated with elevated hs‐CRP levels with AGT C allele as the significant factor for patients with hs‐CRP level of more than 1 mg/L.

Associations of Arsenic Exposure in Drinking Water and Renin–Angiotensin–Aldosterone System Related Gene Polymorphisms with Chronic Kidney Disease

Background/Aim: Both arsenic and the renin–angiotensin–aldosterone system may play a role in kidney damages, and therefore, we conducted a study in Taiwan to evaluate whether arsenic exposure in drinking water and angiotensinogen (AGT) genetic polymorphisms are associated with the risk of chronic kidney disease (CKD). Methods: We conducted a case-control study and recruited 228 patients of CKD and 125 controls without CKD were from the National Cheng Kung University Hospital. All the participants were interviewed using a standard questionnaire to collect data on demographics, lifestyle factors such as cigarette smoking, alcohol, drinking water history, and other relevant risk factors for CKD. Polymorphisms of AGT (A[−20]C) and (Thr174Met) were examined by polymerase chain reaction-restricted fragment length polymorphism. The arsenic level in drinking water of each participant was assessed on the basis of the measurement in 311 townships obtained by a nationwide survey. Results: The frequency of AGT(A[-20]C) A/A genotype in case and control groups was 71.9% and 77.7%, and that of A/C genotype was 28.1% and 22.3%, respectively. In the case and control groups, the frequencies of AGT(Thr174Met) Thr/Thr genotype (78.5% vs. 81.3%), Thr/Met genotype (20.5% vs. 18.8%), and Met/Met genotype (0.0% vs. 1.0%) were similar. However, the distributions of arsenic levels were different between the two groups; while 52.7% of the cases were from townships with high arsenic level, only 35.2% of the controls were from those townships. Conclusions: While AGT(A[-20]C) A/C genotype was more prevalent in patients with CKD, the distribution of AGT(Thr174Met) genotypes has no association with CKD. Arsenic levels in drinking water was also associated with CKD.