Abstract-Recently, a novel mutation in the promoter region of the angiotensinogen gene that involves the presence of an adenine instead of a guanine 6 bp upstream from the transcription initiation site (A Ϫ6 G) has been shown to induce an increase in gene transcription. The aim of this study was to determine the prevalence of the A Ϫ6 G mutation in essential hypertensive patients and to correlate it with aldosterone and renin activity levels. We studied 191 hypertensives. We measured levels of aldosterone (plasma and urinary) and plasma renin activity. We determined the variants A and G using a mutagenically separated polymerase chain reaction technique. In 191 hypertensives, the A variant was detected in 266 of 382 (69.6%) and the G variant in 116 of 382 alleles (30.4%). Plasma aldosterone was significantly higher in patients homozygous for AA than in those homozygous for GG (369Ϯ208 versus 246Ϯ142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4Ϯ39.4 versus 50.8Ϯ25.2 and 37.4Ϯ22.3 nmol/d, respectively). When the patients were grouped according to the presence or absence of the A allele, the aldosterone levels and the plasma aldosterone/plasma renin activity ratio were significantly higher in patients with the A allele. The presence of the A variant was associated with higher levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through higher transcription activity of the angiotensinogen gene and concomitant aldosterone production. The involvement of the angiotensinogen gene was first suggested by Jeunemaitre et al, 5 who established that there is a genetic linkage to essential hypertension in affected sibships, a greater prevalence of T235 variant among hypertensives than in control subjects, and higher plasma concentrations of angiotensinogen in subjects carrying T235. The T235 variant corresponds to the presence of a threonine instead of a methionine at residue 235 of the angiotensinogen gene.Recently, we demonstrated in a Chilean population a high prevalence of the T235 variant, which was more common in patients with low-renin hypertension. 6 However, it is not yet clear whether the T235 allele directly accounts for the physiological effects or just acts as a marker for other causative mutations. More recently, a common variant in the promoter region of the angiotensinogen gene has been identified that is in complete linkage disequilibrium with the T235 variant. The promoter variant corresponds to the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription (A Ϫ6 G). 7 In vitro experiments have already demonstrated that the guanine-to-adenine substitution at position Ϫ6 affects the basal transcription rate of the angiotensinogen gene. 7 In vivo, the effect of this variant has not been evaluated. The aim of this study was to determine the prevalence of the A Ϫ6 G variant in a Chilean population of essential hypertensive (EH) pati...