Angiotensinogen gene polymorphism near transcription start site and blood pressure: role of a T-to-C transition at intron I.

Molecular variants of the angiotensinogen gene, a key component of the renin-angiotensin system, are considered genetic risk factors for primary hypertension. A relation between the angiotensinogen gene locus and hypertension has been found in whites, Japanese, and African Caribbeans but not in Chinese. The lack of a consistent association between M235T polymorphism at exon 2 and hypertension has suggested that another site in linkage disequilibrium with M235T is the causal mutation. We studied the relations among plasma angiotensinogen concentrations, blood pressure, related clinical variables, and mutations of the 5' upstream core promoter region of the human angiotensinogen gene in 274 subjects recruited from our outpatient clinic. We confirmed that plasma angiotensinogen concentration was significantly correlated with A-20C mutation and percent body fat and found that systolic and diastolic blood pressures were significantly correlated with G-6A and T+68C mutations. These results suggest that mutations near the transcription start site may be associated with increased blood pressure.