Association of angiotensinogen gene polymorphisms with essential hypertension in African-Americans and Caucasians.
OBJECTIVE
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.


CONCLUSIONS
Overall, the present report provides statistical evidence for the association of AGT with essential hypertension.
Markovic
Daniela
D
Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, NY 10021, USA.
Tang
Xiagna
X
Guruju
Mallikarjunrao
M
Levenstien
Mark A
MA
Hoh
Josephine
J
Kumar
Ashok
A
Ott
Jurg
J
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D044465:White People / Q000235:genetics*
D000808:Angiotensinogen