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: 14.95). 10/1999; 100(13):1394-9. DOI: 10.1161/01.CIR.100.13.1394
Source: PubMed

ABSTRACT 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.

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    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.
    Egyptian Journal of Medical Human Genetics 01/2013; 14(1):13–19.
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    ABSTRACT: Whether the 1166 (A/C) polymorphism of the Angiotensin II (AII) type 1 receptor (AT1R) gene does correlate with increased vascular reactivity to AII is unclear. Accordingly we measured the blood pressure response to exogenous AII and determined the 1166A/C AT1R gene polymorphism in patients with Chronic Heart Failure (CHF). 40 patients with CHF and functional capacity compatible with NYHA class II-III were studied. All patients were genotyped for the 1166 A/C polymorphism. The frequency of the C allele was 0.2. Radial Artery Systolic Pressure (RASP) was non- invasively monitored using a Colins Pilot Monitor 9200. Ascending doses of AII were administered intravenously to increase RASP by 20 mmHg (AII Pd 20). Patients with CHF exhibited a 10-fold variability in their response to AII with Pd 20 ranging from 2.5 to 25 ng/kg. Patients with AA or AC/CC genotype, had similar AII Pd 20: 11.35 ± 1.18 vs. 13.21 ± 2.2 respectively (p = 0.42). Similarly, among the patients with decreased vascular reactivity who required ≥ 10 ng/kg of AII to achieve Pd 20 (n = 29), RASP response to 10 ng/kg of AII was comparable among patients with AA and AC/CC genotype 22.5 ± 2.8 vs. 21.9 ± 3.3 mmHg respectively (p = 0.9). In patients with CHF, the doses of AII required to increase BP by 20 mmHg demonstrate a 10-fold variability. The 1166A/C polymorphism of the AT1R gene does not account for the wide range of AII Pd 20. Factors other than 1166A/C polymorphism of the AT1R gene are likely to determine BP response to exogenous AII in CHF patients. J Clin Basic Cardiol 2001; 4: 75-77.