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(Circulation. 2007;115:725-732.)
© 2007 American Heart Association, Inc.

Hypertension

Association Between Angiotensinogen, Angiotensin II Receptor Genes, and Blood Pressure Response to an Angiotensin-Converting Enzyme Inhibitor

Xiaowen Su, MD; Liming Lee, MD, MPH; Xiaohui Li, MD; Jun Lv, PhD; Yonghua Hu, MD; Siyan Zhan, MD, PhD; Weihua Cao, MD, MPH; Ling Mei, MD; Yong-Ming Tang, PhD; Dai Wang, PhD; Ronald M. Krauss, MD; Kent D. Taylor, PhD; Jerome I. Rotter, MD; Huiying Yang, MD, PhD

From the Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, Calif (X.S., X.L., L.M., Y.-M.T., D.W., K.D.T., J.I.R., H.Y.); Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (L.L., J.L., Y.H., S.Z., W.C.); and Children’s Hospital Oakland Research Institute, Oakland, Calif (R.M.K.).

Correspondence to Huiying Yang, MD, PhD, Medical Genetics Institute, 665 West Tower, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 (e-mail huiying.yang{at}cshs.org) or Liming Lee, MD, MPH, Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Center, Dongdan 3 tiao 9 hao, Beijing 100730, PR China (e-mail lmlee@pumc.edu.cn).

Received May 25, 2006; accepted November 30, 2006.

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.

Methods and 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.

Conclusion— 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.

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