ASSOCIATION OF THE ANGIOTENSINOGEN GENE TO SERUM ANGIOTENSINOGEN IN BLACKS AND WHITES

A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon 235 (T235) has been associated with a higher serum angiotens inogen concentration and with hypertension in white subjects. The freq uency of T235 is about two Limes higher in blacks than whites, suggest ing that AGT may contribute to the susceptibility to hypertension in b lacks more than it does in whites. However, an association of T235 wit h angiotensinogen level or blood pressure has not been observed in bla cks. possibly because the high prevalence of T235 makes it insufficien tly informative as a marker. For this reason, we undertook to further differentiate the T235 carrier state by constructing haplotypes with a lleles in the 5' upstream region of AGT. One such haplotype, -1074t;T2 35, showed a significant association with angiotensinogen level in a c ohort 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 w as significantly related to body mass index (P = .0017) and the haplot ype (P = .0001). Within specific race groups, the haplotype was signif icantly related to serum angiotensinogen in both the blacks: (P = .027 7) and whites (P = .0001). The mean level of angiotensinogen was highe r 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 ang iotensin I/L), a difference that was marginally significant (P = .0609 ). In the whites, the level of angiotensinogen was also higher in carr iers of a single copy than in those with no copy (1527.9 +/- 71.2 vers us 1099.2 +/- 20.1 nmol angiotensin I/L) (P = .0003). Serum angiotensi nogen level did not increase with two copies of the haplotype, hut In each racial group, there were only four individuals who were homozygou s. 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 assoc iation of genotype with serum angiotensinogen level and blood pressure in blacks and whites, The findings suggest that ACT may play an impor tant role in blood pressure regulation in both racial groups.