Obective: Molecular variants of angiotensinogen ( AGT) have been linked to essential hypertension, and promoter variants have been shown to alter the transcription rate of AGT in vitro. We employed a case-control study to determine whether single nucleotide polymorphisms ( SNPs) in the promoter region of AGT were associated with hypertension in African-Americans and Caucasians. Methods: The frequencies of the variants at base positions - 6, - 20, - 217, - 793, and - 776, both alone and in combination ( haplotypes), were compared between cases and controls in samples stratified based on race and sex. A logistic regression model was applied to test whether AGT genotypes were significant predictors of the disease while adjusting for race, sex, and age. Results: Subjects with the AA or AG genotype at locus - 793 were significantly more likely to have the disease ( OR = 1.88, 95% CI = 1.12 - 3.15). Additionally, the differences in haplotype frequency distributions between cases and controls were significant at the 7% level for all four subgroups ( stratified by race and sex) after adjusting for multiple testing. Based on the odds ratios for each individual haplotype, the haplotype AAAAT ( nucleotide sequences at base positions - 6, - 20, - 217, - 793, - 776) in African-American males, African-American females, and Caucasian females may confer susceptibility to the disease in these population subsets. Conclusion: Overall, the present report provides statistical evidence for the association of AGT with essential hypertension. Copyright (c) 2005 S. Karger AG, Basel.