Association between angiotensinogen, angiotensin II receptor genes, and blood pressure response to an angiotensin-converting enzyme inhibitor.
BACKGROUND
To identify the genetic contribution to the variation in blood pressure (BP) response to angiotensin-converting enzyme inhibitors (ACEIs), single-nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT), angiotensin receptor 1 (AGTR1), and angiotensin receptor 2 (AGTR2) genes were evaluated for their association with BP response to ACEI in Chinese patients with hypertension in a 2-stage design.


RESULTS
We selected 1447 hypertensive patients from a 3-year benazepril postmarket surveillance trial and genotyped them for 14 SNPs in the AGT, AGTR1, and AGTR2 genes. The AGT rs7079 (C/T) SNP (3'-untranslated region) was significantly associated with the response of diastolic BP to benazepril (diastolic BP response: -7.4 mm Hg for subjects with the CC genotype, -8.9 mm Hg for CA, and -10.1 mm Hg for AA; P=0.001). Although there was no association of individual SNPs in the AGTR1 gene, there was a graded response between common haplotypes and systolic BP reduction in the order of haplotype 2 (H2)/lack of haplotype 3 (non-H3) (-13.6 mm Hg) > non-H2/non-H3 (-10.9 mm Hg) > H3/non-H2 (-6.6 mm Hg) (P=0.004). The total variations in response to ACEI therapy that were explained by the AGT SNP and AGTR1 haplotype groups were 13% for systolic and 9% to 9.6% for diastolic BP, respectively.


CONCLUSIONS
AGT SNP rs7079 and AGTR1 haplotypes were associated with BP reduction in response to ACEI therapy in hypertensive Chinese patients. This will be useful in future studies, providing genetic markers to predict the hypertensive response to ACEI therapy.
Su
Xiaowen
X
Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
Lee
Liming
L
Li
Xiaohui
X
Lv
Jun
J
Hu
Yonghua
Y
Zhan
Siyan
S
Cao
Weihua
W
Mei
Ling
L
Tang
Yong-Ming
YM
Wang
Dai
D
Krauss
Ronald M
RM
Taylor
Kent D
KD
Rotter
Jerome I
JI
Yang
Huiying
H
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics*; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; C044946:benazepril