1166 A/C polymorphism of the angiotensin II type 1 receptor gene and the response to short-term infusion of angiotensin II.
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.
- SourceAvailable from: InTech02/2012; , ISBN: 978-953-51-0173-4
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ABSTRACT: Most non-significant individual single nucleotide polymorphisms (SNPs) were undiscovered in hypertension association studies. Their possible SNP-SNP interactions were usually ignored and leaded to missing heritability. In present study, we proposed a particle swarm optimization (PSO) algorithm to analyze the SNP-SNP interaction associated with hypertension. Genotype dataset of eight SNPs of renin-angiotensin system genes for 130 non-hypertension and 313 hypertension subjects were included. Without SNP-SNP interaction, most individual SNPs were non-significant difference between the hypertension and non-hypertension groups. For SNP-SNP interaction, PSO can select the SNP combinations involving different SNP numbers, namely the best SNP barcodes, to show the maximum frequency difference between non-hypertension and hypertension groups. After computation, the best PSO-generated SNP barcodes were dominant in non-hypertension in terms of the occurrences of frequency differences between non-hypertension and hypertension groups. The OR values of the best SNP barcodes involving 2-8 SNPs were 0.705-0.334, suggesting that these SNP barcodes were protective against hypertension. In conclusion, this study demonstrated that non-significant SNPs may generate the joint effect in association study. Our proposed PSO algorithm is effective to identify the best protective SNP barcodes against hypertension.Molecular Biology Reports 05/2013; · 2.51 Impact Factor
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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.