SERUM ANGIOTENSINOGEN CONCENTRATION IN RELATION TO GONADAL-HORMONES, BODY-SIZE, AND GENOTYPE IN GROWING YOUNG-PEOPLE

Multiple factors are thought to influence the level of circulating ang iotensinogen (AGT). We showed previously that the serum AGT concentrat ion was significantly related to body mass index (BMI) in a cohort of young people. In the present study, we studied whether levels of the g onadal hormones estradiol and testosterone might also predict the AGT level and might contribute to the BMI effect, since both the productio n of these hormones and BMI increase with age. In boys (n=127; mean+/- SD age, 14.7+/-1.9 years) and girls (n=104; age, 14.8+/-1.9 years) stu died as a single group, we found a significant association of AGT leve l with level of estradiol (P=0.015) after adjustment for haplotype, ag e, race, testosterone concentration, and BMI. In girls studied alone, the level of AGT showed a significantly positive relation to level of testosterone (P=0.043), possibly a result of peripheral conversion of testosterone to estradiol, after adjustment for haplotype, age, race, estradiol concentration, and BMI. In boys, on the other hand, the leve l of testosterone was inversely related to AGT concentration (P=0.019) , again after making adjustments for the other variables. Finally, in pairs of subjects matched for BMI, age, race, and gender where 1 membe r of each pair had either 1 or 2 copies of an AGT gene haplotype (T235 and -1074t) and the other member had no copy, the level of AGT was hi gher in the carrier of a haplotype in 24 of the 34 pairs (P<0.001). In conclusion, gonadal hormones are an additional influence on the circu lating level of AGT in growing young people. In addition, with matchin g for BMI and other covariates, there is a strong association of AGT g enotype with the serum level of AGT, emphasizing the importance of AGT gene expression as a determinant of the circulating level of AGT.