September 1, 1998Open Access
View Full PaperAngiotensinogen Genotype, Sodium Reduction, Weight Loss, and Prevention of Hypertension
Structured PICO
Does sodium reduction or weight loss reduce the incidence of hypertension in subjects with high-normal diastolic blood pressure, and is this effect modified by angiotensinogen genotype?
P
Population
1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention, with diastolic blood pressures between 83 and 89 mm Hg, genotyped at the angiotensinogen locus.
I
Intervention
Sodium reduction, weight loss, or combined intervention (assigned in a 2x2 factorial design).
C
Comparator
Usual care.
O
Outcome
3-year incidence rate of hypertension.surrogate
The angiotensinogen genotype at position -6 may modify the blood pressure response and hypertension prevention benefits of sodium reduction and weight loss.
Abstract
The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval 0.87, 2.34, test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 0.34, 0.98 versus usual care) but not for persons with the GG genotype (relative risk=1.2 0.79, 1.81, test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension.