Published Online
on April 14, 2003

A more recent version of this article appeared on May 1, 2003

This Article Full Text (PDF) All Versions of this Article: 41/5/1027    most recent 01.HYP.0000068681.69874.CBv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, X. Articles by Chakravarti, A. Search for Related Content PubMed PubMed Citation Articles by Zhu, X. Articles by Chakravarti, A. Related Collections Clinical Studies Genetics of cardiovascular disease

Submitted on December 16, 2002
Revised on January 16, 2003

Associations Between Hypertension and Genes in the Renin-Angiotensin System

Xiaofeng Zhu^*; Yen-Pei C. Chang; Denise Yan; Alan Weder; Richard Cooper; Amy Luke; Donghui Kan; and Aravinda Chakravarti

From the Department of Preventive Medicine and Epidemiology, Loyola University Stritch School of Medicine (X.Z., R.C., A.L., D.K.), Maywood, Ill; the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine (Y.-P.C.C., D.Y., A.C.), Baltimore, Md; and the Division of Hypertension, University of Michigan School of Medicine (A.W.), Ann Arbor, Mich.

^* To whom correspondence should be addressed. E-mail: xzhu1{at}lumc.edu.

Abstract--The genes of the renin-angiotensin system have been subjected to intense molecular scrutiny in cardiovascular disease studies, but their contribution to risk is still uncertain. In this study, we sampled 192 African American and 153 European American families (602 and 608 individuals, respectively) to evaluate the contribution of variations in genes that encode renin-angiotensin system components of susceptibility to hypertension. We genotyped 25 single-nucleotide polymorphisms in the renin-angiotensin system genes ACE, AGT, AGTR1, and REN. The family-based transmission/disequilibrium test was performed with each single-nucleotide polymorphism and with the multilocus haplotypes. Two individual single-nucleotide polymorphisms were significantly associated with hypertension among African Americans, and this result persisted when both groups were combined. The associations were confirmed in haplotype analysis for REN, AGTR1, and ACE in African Americans. Consistent but less significant evidence was found in European Americans. We also randomly sampled unrelated individuals across families to obtain 84 cases and 108 controls among the African Americans and 41 cases and 113 controls in the European Americans. Single-nucleotide polymorphism and haplotype analyses again showed consistent, albeit weaker, results. Thus, in this biracial population sample, we find evidence that interindividual variation in the renin-angiotensin system genes contributes to hypertension risk.

Key words: hypertension, genetic • angiotensin-converting enzyme • haplotypes • angiotensin • renin-angiotensin system • case-control studies

This article has been cited by other articles:

				V. Ramachandran, P. Ismail, J. Stanslas, N. Shamsudin, S. Moin, and R. Mohd Jas Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects Journal of Renin-Angiotensin-Aldosterone System, December 1, 2008; 9(4): 208 - 214. [Abstract] [PDF]

				N. Moore, P. Dicker, J. K. O'Brien, M. Stojanovic, R. M. Conroy, A. Treumann, E. T. O'Brien, D. Fitzgerald, D. Shields, and A. V. Stanton Renin Gene Polymorphisms and Haplotypes, Blood Pressure, and Responses to Renin-Angiotensin System Inhibition Hypertension, August 1, 2007; 50(2): 340 - 347. [Abstract] [Full Text] [PDF]

				X. Su, L. Lee, X. Li, J. Lv, Y. Hu, S. Zhan, W. Cao, L. Mei, Y.-M. Tang, D. Wang, et al. Association Between Angiotensinogen, Angiotensin II Receptor Genes, and Blood Pressure Response to an Angiotensin-Converting Enzyme Inhibitor Circulation, February 13, 2007; 115(6): 725 - 732. [Abstract] [Full Text] [PDF]

				M. E. Dickson and C. D. Sigmund Genetic Basis of Hypertension: Revisiting Angiotensinogen Hypertension, July 1, 2006; 48(1): 14 - 20. [Full Text] [PDF]

				B. Baudin Polymorphism in angiotensin II receptor genes and hypertension Exp Physiol, May 1, 2005; 90(3): 277 - 282. [Abstract] [Full Text] [PDF]

				Y. Dong, X. Wang, H. Zhu, F. A. Treiber, and H. Snieder Endothelin-1 Gene and Progression of Blood Pressure and Left Ventricular Mass: Longitudinal Findings in Youth Hypertension, December 1, 2004; 44(6): 884 - 890. [Abstract] [Full Text] [PDF]

				S.-J. Wu, F.-T. Chiang, W. J. Chen, P.-H. Liu, K.-L. Hsu, J.-J. Hwang, L.-P. Lai, J.-L. Lin, C.-D. Tseng, and Y.-Z. Tseng Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis Physiol Genomics, April 13, 2004; 17(2): 79 - 86. [Abstract] [Full Text] [PDF]

				A. Siani, P. Russo, F. Paolo Cappuccio, R. Iacone, A. Venezia, O. Russo, G. Barba, L. Iacoviello, and P. Strazzullo Combination of Renin-Angiotensin System Polymorphisms Is Associated With Altered Renal Sodium Handling and Hypertension Hypertension, March 1, 2004; 43(3): 598 - 602. [Abstract] [Full Text] [PDF]