A NUCLEOTIDE SUBSTITUTION IN THE PROMOTER OF HUMAN ANGIOTENSINOGEN ISASSOCIATED WITH ESSENTIAL-HYPERTENSION AND AFFECTS BASAL TRANSCRIPTION IN-VITRO

In earlier studies, we provided statistical evidence that individual d ifferences in the angiotensinogen gene, the precursor of the vasoactiv e hormone angiotensin II, constitute inherited predispositions to esse ntial hypertension in humans (1). We have now identified a common vari ant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder, Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleo tide substitution affects the basal transcription rate of the gene. Th ese observations provide some biological insight about the possible me chanism of a genetic predisposition to essential hypertension; they ma y also have important evolutionary implications.