Angiotensin II Type 1 Receptor Genotype Research Articles

Angiotensin II type I receptor gene polymorphism in essential hypertensive and normotensive subjects

Hypertension is a polygenic disorder that involves a complex interplay of genetic and environmental factors. Genes that influence the renin–angiotensin–aldosterone system (RAAS) appear to be particularly important among the many potential candidate components of EHT. The RAAS system plays an important role in BP regulation by maintaining vascular tone and renal hemodynamics. Most of these are mediated via the activation of the angiotensin II type 1 receptor (AT1R). Untreated hypertension increases the risk of developing cardiovascular diseases such as stroke, myocardial infarction, ischemic heart disease, and, target organ damage. A polymorphism in the 3’ untranslated region of the AT1R gene has been described with either an adenine (A) or a cytosine (C) base (A/C transversion) at the 1166 position that is associated with increased blood pressure. A total of 170 hypertensive patients and 170 normal subjects were included in the present study. Genomic DNA was isolated from peripheral blood leukocytes, amplified with PCR, and separated with gel electrophoresis to determine the AT1R genotype. On electrophoresis, the genotypes A/A-359 bp, A/C-220+139 bp, and C/C-220, 139, and 359 bp were identified. In hypertensive patients, the CC genotype was present in 21.18 percent (n = 36) as compared to 11.76 percent (n = 20) in non-hypertensive patients. In this study AT1R CC homozygote was significantly associated with hypertension (p = 0.019). The odds ratio related to the association of the prevalence of the CC genotype with hypertension was 2.014 (95% CI: 1.112–3.650).: From the present study, it is concluded that AT1R gene polymorphism is associated with hypertension, and with the CC genotype, the risk of hypertension increases in comparison to AC and AA. A allele is not significantly associated with hypertension, but the recessive and co-dominant modes of inheritance of allele C (CC) and its co-dominant mode (AC) are a genetic predisposition to hypertension.

Risk and severity of psoriasis vulgaris in relation to angiotensin II type 1 receptor gene polymorphism and metabolic syndrome.

BackgroundPsoriasis vulgaris is a chronic inflammatory and proliferative skin disease, characterized by the formation of itchy, erythematous skin patches or plaques. Patients with psoriasis are at an increased risk of developing metabolic syndrome, including obesity, hypertension, diabetes, and atherosclerosis. Recently, angiotensin II (Ang II) has been reported to be associated with the development of psoriasis. Ang II not only increases the blood pressure but is also a potent proinflammatory modulator and functions through interaction with angiotensin II type 1 receptor (AT1R). Moreover, it is hypothesized that the AT1R gene expression could be correlated with the severity of psoriasis and/or metabolic syndrome.AimWe examined the association of Ang II type 1 receptor (AT1R) A1166C gene polymorphisms and metabolic syndrome with the severity of psoriasis.Patients and methodsThe present case-control study included 25 patients with psoriasis vulgaris and 25 healthy subjects in Egypt. The psoriasis lesions in the patient group were assessed using the psoriasis area and severity index (PASI) score. The AT1R polymorphism A1166C (rs5186) was studied using restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) amplification of the gene from the whole blood sample in both groups. Serum lipid profile and blood sugar levels were assessed post 12 h and 8 h fasting, respectively, in both groups. The severity of metabolic syndrome was evaluated using the severity score.ResultsThe results of the present study demonstrated that the AT1R A1166C gene polymorphisms increased the risk of developing psoriasis in the Egyptian population. We found that 70% of patients with AC genotype and 100% of patients CC genotype reported a PASI score >20 and were considered to be severe cases with a statistically significant difference as compared with patients with AA genotype (p=0.003). In addition, a high statistically significant difference (p=0.001) existed among AT1R genotypes with respect to the percentage of metabolic syndrome in psoriasis patients. Similarly, a statistically significant difference (p=0.004) among AT1R genotypes with respect to metabolic score was found, with the highest level of score and percentage observed in patients with CC genotype than in patients with AC genotype. The lowest level was present among those with AA genotype.ConclusionPatients with psoriasis expressing the C allele of AT1R1166 are susceptible to developing metabolic syndrome and have higher PASI scores as compared with patients carrying the A allele.

Susceptibility and progression of end stage renal disease are not associated with angiotensin II type 1 receptor gene polymorphism

Context: The role of the angiotensin II type 1 receptor (AT1R) gene polymorphism, A1166C, has been shown to be associated with end stage renal disease (ESRD) and its progression. There is also some evidence that HLA class II alleles are associated with ESRD independent of other factors. Objective: To examine the association between AT1R gene polymorphism in the susceptibility and progression to ESRD in patients with chronic renal failure and to investigate if the AT1R genotypes and HLA-DR alleles predict the time to ESRD. Materials and methods: Genotyping was performed in 50 ESRD patients and 44 control subjects for the AT1R A1166C gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ESRD patients were examined for HLA-DRB1 alleles according to a reverse hybridization line probe assay. Results: Allele and genotype frequencies of the AT1R polymorphism did not differ significantly between ESRD patients and controls. Furthermore, there was no association between the AT1R gene polymorphism or HLA-DRB1 alleles with the time to the occurrence of end stage failure. Discussion and Conclusion: We concluded that the AT1R genotype does not contribute to the genetic susceptibility of ESRD and is not associated with progression of chronic kidney failure to ESRD.

Association of angiotensin I converting enzyme, angiotensin II type 1 receptor and angiotensin I converting enzyme 2 gene polymorphisms with the dyslipidemia in type 2 diabetic patients of Chinese Han origin.

To investigate whether the genetic polymorphisms in the angiotensin I converting enzyme (ACE) (insertion/ deletion, or I/D), angiotensin II type 1 receptor (AT1R) (rs5186), and ACE2 (rs2285666) could be associated with dyslipidemia in Type 2 diabetic (T2D) patients of Chinese Han origin. The above 3 polymorphisms were genotyped in a total of 282 patients with T2D and dyslipidemia (Group A), 182 patients with T2D but without dyslipidemia (Group B), and 324 healthy controls. The association between a certain polymorphism and each group was assessed by an odds ratio (OR). The D allele of the ACE (I/D) was significantly associated with the risk of T2D accompanying dyslipidemia between group A and controls [OR=1.37, 95% confidence interval (CI)=1.08-1.74; p=0.010], and significant association of the D allele with dyslipidemia was also observed in diabetic patients (OR=1.88, 95% CI=1.40-2.54; p<0.001). Furthermore, the ID genotype had a decreased risk of developing T2D without dyslipidemia as compared with controls (OR=0.52, 95% CI=0.32-0.82; p=0.0060). The distributions of the AT1R (rs5186) and ACE2 (rs2285666) genotypes and alleles did not differ between T2D patients with or without dyslipidemia and the controls. This study demonstrates that the ACE (I/D) polymorphism is associated with T2D, regardless of the absence or presence of dyslipidemia. The polymorphisms in the AT1R (rs5186) and ACE2 (rs2285666) seem to play lesser roles in the development of T2D.

Association of angiotensin I converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms with breast cancer prognostic factors in iranian population

It has been indicated that renin-angiotensin system (RAS) has role in various steps of cancer progression. The presence of RAS components has been shown in normal and breast cancer tissue. insertion/deletion (I/D) is one of angiotensin I converting enzyme (ACE) polymorphisms and A1166C is one of angiotensin II type-1 receptor (AT1R) polymorphisms which have been associated with various diseases such as cardiovascular diseases. In the present study, we aimed to substantiate the putative significance of ACE and AT1R on breast cancer biology by investigating the influence of their gene polymorphisms on breast cancer progression. The I/D and A1166C polymorphisms were evaluated by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), respectively in 70 breast cancer patients diagnosed with invasive breast cancer and 70 healthy women. Breast cancer prognostic factors were obtained from medical and pathology reports of patients. There was no significant difference between cases and controls for ACE (I/D) (P = 0.15) and AT1R (A1166C) genotypes (P = 0.86). In breast cancer patients, when DD genotype was used as reference group, the combination of II and ID genotypes was associated with increased HER-2 expression (P = 0.020; OR, 4.58; 95% CI, 1.26-16.60). Also, when AA genotype was used as reference group, the AC genotype was associated with higher tumor TNM stage (P = 0.024; OR, 4.66; 95% CI, 1.18-18.35). This is the first study indicating that ACE (I/D) polymorphism is associated with HER-2 expression and AT1R (A1166C) polymorphism is associated with tumor TNM stage in breast cancer patients.

Relation between AT1R Gene Polymorphism and Long-Term Outcome in Patients with Heart Failure

Objectives: Angiotensin II plays a key role in the pathophysiology of heart failure (HF). This study examined the angiotensin II type 1 receptor (AT1R) polymorphism in patients with systolic HF and its relation to clinical manifestations and patient outcome. Methods: We genotyped 134 patients with HF and reduced systolic function for the AT1R A1166C genotype using polymerase chain reaction and restriction fragment length polymorphism. We analyzed the relationship between the AT1R A1166C polymorphism and clinical, electrocardiographic, echocardiographic and laboratory parameters in patients with ischemic and non-ischemic etiology and examined the relation between the AT1R genotype and long-term (30 months) patient survival. Results: In HF patients, frequency of the AT1R 1166C allele and specifically the CC genotype was similar to the general population, but associated with an ischemic and not a non-ischemic etiology (p = 0.02). The CC genotype was associated with more advanced disease and more severe abnormalities of renal function (p = 0.008). Survival analysis showed that AT1R CC homozygous patients had significantly higher mortality (p = 0.008; adjusted odds ratio for mortality 6.35, 95% confidence interval 1.49–11.21, p = 0.01). Conclusion: The CC AT1R genotype was associated with poor prognostic markers and increased mortality. The findings support the principle of genome-based therapies in the future treatment of HF patients.

Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism and Its Association with Preeclampsia in Chinese Women

Objective: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. Methods: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT1R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. Results: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. Conclusion: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.

The Effect of Angiotensin II Type‐1 Receptor Gene Polymorphisms on Doppler Blood Flow Parameters of Carotid and Brachial Arteries in Patients with Myocardial Infarction

Genetic influence on Doppler blood flow parameters of carotid and brachial arteries (BA) is uncertain. We investigated the relationship between the angiotensin II type-1 receptor (AT1R) gene polymorphism and the blood flow characteristics of common carotid arteries (CCA) and BA by color Doppler ultrasound (CDUS) in patients with a first anterior acute myocardial infarction (AMI). Sixty-seven patients (15 women and 52 men), aged 25-77 years, with anterior AMI were studied. The AT1R genotypes were established. Based on the polymorphism of the AT1R, they were classified into three groups: AT1R AA genotype (Group1, n = 42 patients), AT1R AC genotype (Group 2, n = 17 patients), and AT1R CC genotype (Group 3, n = 8 patients). Peak-systolic velocity (PSV) and end-diastolic velocity (EDV) of right and left CCA, PSV of right BA, and intimal-medial thickness (IMT) of both CCA were measured by CDUS. All results evaluated statistically. The AT1R genotypes were distributed as follows: 63% AA, 25% AC, and 12% CC. PSV of BA and both CCA were higher in patients with CC and AC than AA (P < 0.05). Also, IMT of both CCA were also higher in the same groups (P < 0.05). Our results suggest that AT1R gene polymorphism influences Doppler blood flow parameters of both BA and CCA, and IMT of CCA. Although further studies are required.

Gene Polymorphisms of Angiotensin II Type 1 Receptor and Angiotensin-Converting Enzyme in Two Ethnic Groups Living in Zhejiang Province, China

Polymorphisms of ACE insertion/deletion (I/D) and angiotensin II type 1 receptor (AT1R) 1166A-C have been associated with many diseases, and distributions of their genotypes vary in different races and populations. The aim of this study was to investigate distributions of angiotensin-converting enzyme (ACE) and AT1R genotypes in Han and She populations in ZheJiang province. We determined ACE and AT1R genotypes in 189 Han and 163 She individuals. DNA was extracted from peripheral blood samples. Analyses of ACE and AT1R genotypes were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The frequencies of ACE genotypes and alleles among the Han sample (41.3%II, 41.3%ID, 17.5%DD; 61.9%I allele, 38.1%D allele) were similar to those among She individuals (39.9%II, 39.3%ID, 20.9%DD; 59.5%I allele, 40.5%D allele), with p=0.660; p=0.421. However, significant differences in the distributions of ACE polymorphism between men and women among She population were observed, with p=0.042, p=0.014. AT1R genotype and allele frequencies in the Han population were (88.4%AA, 11.1%AC, 0.5%CC) and (93.9%A allele, 6.1%C) allele respectively. In the She population they were (78.0%AA, 21.3%AC, 0.6%CC) and (89.0%A allele, 11.0%C allele). The significant differences were found between Han and She populations with p=0.031, p=0.018, and within subgroups of women, with p=0.010, p=0.021. There were no significant differences within subgroups of men (p=0.476, p=0.261). The genotype distributions or allele frequencies of ACE and AT1R were significantly different between the samples of the She and Han populations.

Association between Angiotensin II Type 1 Receptor Gene Polymorphism and Essential Hypertension: the Ohasama Study

Gene targeting approaches have suggested that the angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C) is associated with hypertension in Caucasians, but not in Japanese. The goal of this study, the Ohasama Study, was to examine the association between AT1R/A1166C and hypertension, especially home BP, in the Japanese general population. The Ohasama Study was a cohort study based on Japanese rural residents of Ohasama Town in the northern part of Japan. Subjects who gave informed consent to the study protocol and genetic analysis were recruited. Home BP was measured twice in the morning within 1 h of waking up and in the evening just before going to bed. The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA 84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics among the AT1R genotypes (AA, AC, CC). In the subjects not receiving antihypertensive medication (n =817), both casual BP and home BP were not different among the AT1R genotypes after adjusting for confounding factors (age, sex, body mass index, current smoking habit and current alcohol consumption). The frequency of hypertension showed no difference among AT1R genotypes after adjusting for confounding factors, though the AC and CC genotypes were more frequent in hypertensives than in normotensives. Our data suggested that the AT1R/A1166C polymorphism is not a major genetic predisposing factor for hypertension in Japanese.

Interactions between gender and the angiotensin type 1 receptor gene polymorphism

The cardiovascular effects of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R); one polymorphism of the AGT1R gene, A1166-->C, has been associated with hypertension. The hemodynamic response to angiotensin II is blunted in women compared to men, but interactions between gender, blood pressure, and AGT1R gene polymorphisms are unclear. A total of 81 young healthy normotensive individuals maintained regulated sodium and protein intake prior to study. They were divided into four groups based on gender and A1166-->C genotype (AA versus AC/CC); serial supine blood pressures were obtained. A subset of 52 individuals received graded infusions of angiotensin II. Inulin and paraaminohippurate clearance techniques were used to measure renal hemodynamic function at baseline and in response to the infusions. Men with the AC/CC genotype exhibited higher blood pressures than men with the AA genotype; however, this relationship was not found among women. Analysis of covariance revealed a significant interaction between gender and AGT1R genotype in the determination of blood pressure. Glomerular filtration rate (GFR) declined variably in the study subjects following infusion of angiotensin II, and a statistical model incorporating gender and genotype best predicted the fall in GFR. There was a trend for females of the AA genotype to have a greater fall in GFR in response to angiotensin II infusion, than any of the other groups. In young healthy subjects, there is an important interaction between gender, the AGT1R A1166-->C gene polymorphism, and blood pressure. In addition, the renal hemodynamic response to angiotensin II infusion is a function of both gender and the AGT1R genotype.

Influence of angiotensinogen M253 T gene polymorphism and an angiotensin converting enzyme inhibitor on restenosis after percutaneous coronary intervention

We studied the relation between renin-angiotensin system (RAS) related gene polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion ( I/ D), angiotensinogen (AGT) M253 T and angiotensin II type 1 receptor (AT1R) A1166 C, and the effect of quinapril, an ACE inhibitor with high tissue-binding affinity, on preventing restenosis after percutaneous coronary intervention (PCI). A total of 253 patients successfully treated for coronary artery disease were randomly assigned to quinapril or control. Of the 215 patients who completed the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions who provided blood samples for genotype determination. In the control, the ACE D homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up ( P=0.063). The other two genotypes of AGT and AT1R did not affect restenosis after PCI. According to quinapril treatment, the AGT T homozygotes significantly showed a beneficial effect of quinapril on MLD ( P=0.013) and late lumen loss ( P=0.013). The ACE I homozygotes also exhibited beneficial effects of quinapril on larger MLD ( P=0.065). The AT1R genotype did not influence the quinapril effect. In conclusion, the AGT T homozygotes might benefit from effects of quinapril on preventing restenosis after PCI.

Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with...

Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.