Multiple Polymorphisms in the renin- angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort.
OBJECTIVE
When compared with other U.S. populations, African Americans have excess hypertension. Genetic variants in elements of the renin-angiotensin-aldosterone system (RAAS), namely the angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), and angiotensin II type 1 receptor (AGTR1) genes, have been associated with risk of hypertension in some populations.


METHODS
We genotyped the D/I polymorphism in the ACE gene, the C(-344)T polymorphism in the CYP11B2 gene, and the C(-535)T polymorphism in the AGTR1 gene among African American and Latino members of the Multiethnic Cohort Study (MEC) to determine their association with hypertension.


RESULTS
We observed no significant increase in the risk of hypertension for either African Americans or Latinos homozygous or heterozygous for the D allele of the ACE gene. Among African Americans we observed carriers of the (-344)T allele of CYP11B2 to be at increased risk of hypertension (versus CC genotype: TC genotype, OR = 1.66 [95% CI: 1.01-2.72]; TT genotype, OR = 1.74 [95% CI: 1.07-2.82]). There was also an increase in risk of hypertension associated with the AGTR1 T allele for African Americans (versus CC genotype: TC genotype, OR = 2.62 [95% CI: 1.46-4.72]; TT genotype, OR = 2.67 [95% CI: 1.51-4.74]). The associations observed with CYP11B2 and AGTR1 genotypes were not observed among Latinos.


CONCLUSIONS
These data suggest that the (-535)T allele of AGTR1 and (-344)T allele of CYP11B2 may increase hypertension risk among African Americans but not among Latinos. Characterization of the linkage disequilibrium and haplotype patterns in the RAAS pathway genes will be crucial to understanding differences in hypertension susceptibility in these ethnic populations.
Henderson
Sean O
SO
Department of Emergency Medicine, Keck School of Medicine, University of Southern California Los Angeles, CA 90033, USA. sohender@hsc.edu
Haiman
Christopher A
CA
Mack
Wendy
W
D044383:Black People; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D006973:Hypertension / Q000453:epidemiology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D001741:Black or African American
D044140:Receptor, Angiotensin, Type 1; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A