Angiotensin II type2 (AT2) receptor gene polymorphism and hypertension in the elderly with salty taste disturbance

Abstract

Although hypertension in the elderly is highly dependent on excess intake of sodium, at least partially based on salty taste disturbance, little is known about association of gene polymorphisms with hypertension in the elderly with salty taste disturbance. To clarify the role of gene polymorphisms in this mechanism, 126 elderly female subjects and 61 male subjects were enrolled (mean age + SD; 81 + 7 years) for determination of magnitudes of NaCl (1.25%, 2.5%, 5%, 10% and 20%) in aqueous solution. Thresholds for salty taste were divided into six grades. Non of the subjects took angiotensin-I converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT1) receptor antagonists. We analyzed A1166C polymorphism of human AT1 receptor gene, C3123A polymorphism of AT2 receptor gene mapped on human X chromosome, angiotensinogen M235T polymorphism, and angiotensin-I converting enzyme gene I/D polymorphism. There was a significant (female;p=0.005,male;p=0.040) association (ANOVA) of salty taste threshold with the AT2 receptor gene polymorphism, but not with other polymorphisms. Thus the elderly subject with AA genotype of the AT2 receptor gene required about 2.5 times higher concentration of NaCl solution to detect salty taste compared to those with CC genotype. Moreover, the incidence of hypertension assessed by ambulatory blood pressure measurements (>140/90 mmHg) was significantly (p=0.017) higher in elderly subjects with the AA genotype (63%) than those with AC or CC genotypes (30%) (chi-square). On the other hand, there was significant (p=0.005) correlation (Spearman) between the salty taste threshold and decrease in diastolic blood pressure from the value at ambulatory measurement to that after restriction of salt intake (7 g/day) for 4 weeks. These observations indicate participation of AT2 receptor gene polymorphism in salty taste disturbance and in salt-sensitive increase in blood pressure in elderly patients with hypertension.