Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites

Abstract

A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon 235 (T235) has been associated with a higher serum angiotensinogen concentration and with hypertension in white subjects. The frequency of T235 is about two times higher in blacks than whites, suggesting that AGT may contribute to the susceptibility to hypertension in blacks more than it does in whites. However, an association of T235 with angiotensinogen level or blood pressure has not been observed in blacks, possibly because the high prevalence of T235 makes it insufficiently informative as a marker. For this reason, we undertook to further differentiate the T235 carrier state by constructing haplotypes with alleles in the 5' upstream region of AGT. One such haplotype, -1074t;T235, showed a significant association with angiotensinogen level in a cohort of black and white children and adolescents (76 blacks, mean age = 12.3 +/- 2.0 [SD] years; 139 whites, mean age = 12.4 +/- 1.8 years). With a linear regression model, the level of serum angiotensinogen was significantly related to body mass index (P = .0017) and the haplotype (P = .0001). Within specific race groups, the haplotype was significantly related to serum angiotensinogen in both the blacks (P = .0277) and whites (P = .0001). The mean level of angiotensinogen was higher in the blacks carrying a single copy of the haplotype than in those without the haplotype (1472.2 +/- 68.4 versus 1274.9 +/- 46.7 nmol angiotensin I/L), a difference that was marginally significant (P = .0609). In the whites, the level of angiotensinogen was also higher in carriers of a single copy than in those with no copy (1527.9 +/- 71.2 versus 1099.2 +/- 20.1 nmol angiotensin I/L) (P = .0003). Serum angiotensinogen level did not increase with two copies of the haplotype, but in each racial group, there were only four individuals who were homozygous. The haplotype showed a marginally significant relation (P = .0757) to the mean of longitudinally determined diastolic pressures adjusted for body mass index, race, sex, and age. In summary, using a haplotype to differentiate further the T235 carrier state, we observed an association of genotype with serum angiotensinogen level and blood pressure in blacks and whites. The findings suggest that AGT may play an important role in blood pressure regulation in both racial groups.