235T-variant of the angiotensinogen gene is associated with early-onset of hypertension

Recent studies suggest that the 235T variant of the angiotensinogen gene, associated with increased plasma levels of angiotensinogen, is associated with the development of hypertension in Caucasians. Because genetic forms of hypertension would be expected to develop at an earlier age than hypertension caused primarily by non-genetic factors, we examined the relationship between age-of-onset of hypertension and the angiotensinogen genotype. Age of onset was determined by interview and review of the full medical records of 281 consecutive Caucasian patients with hypertension referred to our hypertension clinic. Thirty individuals with suspected or proven secondary hypertension were excluded from analysis. M235T-genotype was determined by mutagenically-separated allele-specific PCR-amplification of DNA extracted from peripheral leukocytes. While frequency of the 235T-allele (q235T=0.5) was not significantly different from that in a normotensive control group (n=182), this allele was significantly more frequent in patients with onset of hypertension before 50 years of age (n=176, q235T=0.55) than in patients with later onset (n=75, q235T=0.42, p<0.01). Within each age-of-onset group, sex and age distribution as well as duration of hypertension were comparable between the different genotypic groups. These findings support the hypothesis, that the 235T-variant of the angiotensinogen gene may be a marker of an increased genetic risk for the early development of essential hypertension.