Enhanced blood pressure response to mild sodium reduction in subjects with the 235T variant of the angiotensinogen gene

The relationship of high salt intake to elevated blood pressure levels has been demonstrated in most populations by cross-sectional, longitudinal, physiological, and clinical intervention studies. Variation within the angiotensinogen gene has been implicated in the genetic control of blood pressure levels and has been suggested to contribute to increased salt sensitivity. A total of 86 hypertensive men and women who had never been treated and who had participated in a 6-month randomized, placebo-controlled, clinical trial of low-sodium mineral salt (19% reduction in urinary sodium versus 12% increase in placebo group) were genotyped at the angiotensinogen M235T locus to test the hypothesis that the 235T allele is associated with a significant blood pressure response to a sodium reduction intervention whereas the 235M allele is not. After adjustment for gender and baseline blood pressure, persons with the TT and MT genotypes showed significant systolic blood pressure reductions on mineral salt compared with control subjects (P = .02 and P = .001, respectively) but not persons with the MM genotype (P = .10). Net adjusted diastolic blood pressure reductions also showed greater significance for persons with the TT and MT genotypes than for persons with the MM genotype (P = .08, P = .01, and P = .83, respectively). The net adjusted systolic and diastolic blood pressure reduction was -8.6/-3.9 mm Hg for persons with the TT genotype, -9.0/-5.2 mm Hg for the MT genotype, and -5.3/-1.0 mm Hg for the MM genotype. We conclude that the 235T allele of the angiotensinogen gene is associated with greater blood pressure decreases than the 235M allele after a sodium reduction intervention. The angiotensinogen gene accounts for some of the interindividual variation of the blood pressure response to sodium reduction.