A(-6)G variant of angiotensinogen gene and aldosterone levels in hypertensives

Recently, a novel mutation in the promoter region of the angiotensinogen ge ne that involves the presence of an adenine instead of a guanine 6 bp upstr eam from the transcription initiation site (A(-6)G) has been shown to induc e an increase in gene transcription. The aim of this study was to determine the prevalence of the A(-6)G mutation in essential hypertensive patients a nd to correlate it with aldosterone and renin activity levels. We studied 1 91 hypertensives. We measured levels of aldosterone (plasma and urinary) an d plasma renin activity. We determined the variants A and G using a mutagen ically 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 pati ents homozygous for AA than in those homozygous for GG (369+/-208 versus 24 6+/-142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4+/-39.4 versus 50.8+/-25.2 and 37.4+/-22 .3 nmol/d, respectively). When the patients were grouped according to the p resence or absence of the A allele, the aldosterone levels and the plasma a ldosterone/plasma renin activity ratio were significantly higher in patient s with the A allele, The presence of the A variant was associated with high er levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through hig her transcription activity of the angiotensinogen gene and concomitant aldo sterone production.