Angiotensinogen promoter sequence variants in essential hypertension

Background: Essential hypertension is a complex multifactorial disease caused by ill-defined genetic factors. The angiotensinogen (AGT) gene has been implicated as a risk factor in essential hypertension. Methods: To assess the role of AGT in hypertension, we evaluated two polymorphisms (A-6G and C-20A) in the 5' region of the gene that have been shown to have a role in transcriptional regulation. A total of 463 subjects were studied: 243 African Americans (26 male and 34 female normotensives, 66 male and 117 female hypertensives) and 220 whites (35 male and 60 female normotensives, 55 male and 70 female hypertensives). African American and white subjects were examined individually, as significant differences in allele and genotype frequencies were observed between these two cohorts. Results: White female hypertensives and normotensives differed significantly in genotype frequency at C-20A (P =.02). No other single site comparisons were significantly different between hypertensives and normotensives in either the white or African American samples. Haplotype frequencies in white males also differed significantly between phenotypic classes (P =.05). To evaluate the data further, we assessed all polymorphic sites simultaneously by the examination of multisite interaction and determined the single best genetic model for each population. A model that included both sites and gender correctly predicted hypertension status in the white population 59.1% of the time (P =.039). The model generated for the African American population was not significant. Conclusions: Our results suggest that a complex set of a genetic factors interact with gender to predispose whites to hypertension.