1166 A/C Polymorphism of the Angiotensin II Type 1 Receptor Gene and the Response to Short-Term Infusion of Angiotensin II

Department of Medicine/Nephrology, University of Erlangen-Nürnberg, Germany.
Circulation (Impact Factor: 14.43). 10/1999; 100(13):1394-9. DOI: 10.1161/01.CIR.100.13.1394
Source: PubMed


Previous studies reported an association of the 1166 A/C polymorphism of the angiotensin II (Ang II) type 1 receptor gene with high blood pressure and cardiovascular disease. We tested the hypothesis that this polymorphism affects the blood-pressure, renal hemodynamic, and aldosterone response to infused Ang II.
Young, male, white volunteers (n = 116) with normal (n = 65) or mildly elevated (n = 51) blood pressure on a high salt intake were genotyped for the 1166 A/C polymorphism. Two doses of Ang II (0.5 and 3 ng x kg(-1) x min(-1) over 30 minutes each) increased blood pressure, plasma aldosterone, glomerular filtration rate, and filtration fraction and decreased renal blood flow. The blood-pressure, renal hemodynamic, and aldosterone responses were not significantly different between subjects homozygous for the A allele (n = 56) and heterozygous subjects (n = 47) or subjects homozygous for the C allele (n = 13). Comparison of A allele homozygotes with all C allele carriers pooled (n = 60) or restriction of the analysis to normotensive volunteers also revealed no significant differences between genotypes.
The 1166 C variant of the Ang II type 1 receptor does not lead to a greater blood-pressure, aldosterone, or renal vascular response to infused Ang II in young, male, white subjects. We conclude that the 1166 A/C polymorphism does not have a major effect on these actions of Ang II.

5 Reads
  • Source
    • "Hypertension is a multifactorial disorder because of the interaction of many risk genes such as molecular variants of the angiotensinogen gene, angiotensin converting enzyme gene, angiotensin II receptor I gene and the corin gene [1] [2] [3] [4], and environmental factors such as obesity, body mass index (BMI), dietary salt intake, alcohol consumption, stress and high-density lipid (HDL)–cholesterol levels. Genes determine approximately 20–60% of the variability in blood pressure in different populations [4] [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A common molecular variant of the angiotensinogen gene had been reported to predispose some ethnic groups to hypertension. This case–control study was designed to determine the frequency and association of the angiotensinogen M235T allele with hypertension in residents of Calabar and Uyo cities, south–south Nigeria.The study involved 1308 subjects, 612 patients and 696 controls. The M235T variant was investigated using an allele specific polymerase chain reaction and enzymatic digestion to determine allele frequencies. Hypertensinogenic factors such as dietary habits, physical activity, smoking and drinking habits were assessed using questionnaires. Descriptive statistics, chi-square and multiple regression analysis were used to analyze the data obtained.The M235T allele frequency was high (0.94 for hypertensives and 0.96 for controls) though it was not associated with hypertension status. The odds ratio for hypertension was 0.64 (95% confidence interval: 0.39–1.06) there were no significant differences between the genotype frequency of hypertensives and controls. By multiple regression, Hypertension was observed to be associated with age and was a predictor for systolic blood pressure in both patient r2 = 0.359; p < 0.05 and control groups r2 = 0.26.Age and body mass index were predictors for diastolic blood pressure in the control group, r2 = 0.28.Although the frequency of the M235T variant was high, it was not a significant risk factor for hypertension in the study population.
    Full-text · Article · Jan 2013 · Egyptian Journal of Medical Human Genetics
  • Source
    • "Gene-targeting studies using transgenic mice suggested that variants of the human AGTR1 receptor gene that alter its level of expression might likewise affect blood pressure [22] [23]. In this regard, associations between polymorphisms in the human AGTR1 gene and hypertension have been reported with conflicting results [24] [25] [26]. A1166C polymorphism is an extensively investigated variant on relationship between AGTR1 and hypertension. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Essential hypertension is considered to be a multifactorial trait resulting from the combined influence of environmental and genetic determinants. The aim of the study is to assess the association between the human AGTR1 gene and essential hypertension (EH) using a haplotype-based case-control study in Han Chinese subjects. Seven tag SNPs and the A1166C polymorphism of the AGTR1 gene were genotyped in 510 hypertension subjects and 510 normotensive subjects using PCR-RFLP method. Single SNP analyses indicated that the rs12695895 was significantly associated with hypertension, adjusted for covariates. Compared with the other haplotypes, Hap4 (AGGACTT) which carry the susceptible rs12695895 A allele was found to significantly increase the risk of EH with odds ratios equal to 1.84 (p=0.0002). The present results indicate that rs12695895 might be a genetic marker for EH and Hap4 (AGGACTT) was associated with hypertension in Han Chinese population.
    Full-text · Article · Oct 2009 · Clinical biochemistry
  • Source
    • "In the present study, no significant association was found between AT1 and HP in elderly pregnancy, and multivariate analysis also revealed that the association of AT1 with HP was independent of maternal age. It was reported that the A1166C polymorphism does not have a major effect on the actions of angiotensin II (Hilgers et al. 1999), while the polymorphism was found to be associated with salt sensitivity in hypertensive patients (Spiering et al. 2000). Elucidation of whether there is synergism and/or interaction between the AT1 genotype and dietary salt intake during pregnancy in the manifestation of HP will be the next goal of our future studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of "AC+CC genotype of AT1" was significantly higher in severe HP than in the controls. A multivariate analysis with "AC+CC genotype of AT1" and "TT genotype of AGT" revealed that these were independently associated with primiparous severe HP. However, when "family history of hypertension" and "prepregnancy BMI > or =25" were added as factors examined in the multivariate analysis, only "TT genotype of AGT" and "family history of hypertension" were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.
    Full-text · Article · Feb 2004 · Journal of Human Genetics
Show more