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(Hypertension. 2005;46:1294.)
© 2005 American Heart Association, Inc.

Original Articles

A Population Association Study of Angiotensinogen Polymorphisms and Haplotypes With Left Ventricular Phenotypes

Laura J. Rasmussen-Torvik; Kari E. North; C. Charles Gu; Cora E. Lewis; Jemma B. Wilk; Aravinda Chakravarti; Yen-Pei C. Chang; Michael B. Miller; Na Li; Richard B. Devereux; Donna K. Arnett

From the Division of Epidemiology and Community Health (L.J.R.-T., M.B.M.), University of Minnesota, Minneapolis; Department of Epidemiology (K.E.N.), University of North Carolina, Chapel Hill; Division of Biostatistics (C.C.G.), Washington University School of Medicine, Saint Louis, Mo; Division of Preventive Medicine (C.E.L.) and Department of Epidemiology (D.K.A.), University of Alabama at Birmingham; Departments of Neurology and Medicine (J.B.W.), Boston University School of Medicine, Massachusetts; Institute of Genetic Medicine (A.C., Y.-P.C.C.), John Hopkins University School of Medicine, Baltimore, Md; Division of Biostatistics (N.L.), University of Minnesota, Minneapolis; and Division of Cardiology (R.B.D.), Weill Medical College of Cornell University, New York, NY.

Correspondence to Laura J. Rasmussen-Torvik, MPH, Division of Epidemiology and Community Health, University of Minnesota School of Public Health, 1300 S Second St, Suite 300, Minneapolis, MN 55454-1015. E-mail rasm0218{at}umn.edu

Several studies have shown an association between single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene and hypertension. Because hypertension is a risk factor for left ventricular (LV) hypertrophy and because evidence from animal models suggests that AGT may play a role in the growth and hypertrophy of the heart, we chose to conduct a population association study examining the relationship of 10 SNPs in the AGT gene with 7 different LV phenotypes measured by echocardiography. Participants (336 whites and 441 blacks) were drawn from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Individuals were genotyped for 10 previously identified SNPs within the AGT gene. SNP genotype results were regressed against continuous LV phenotypes to test associations separately in each race. Using a cutoff of P<0.005 to account for multiple testing, we found 1 SNP (rs943580) significantly associated with transmitral early peak filling velocity (MVE) in the black population. We also used Phase 2.0.2 to reconstruct haplotypes from genotype data. Using the same cutoff of P<0.005, we found no haplotypes to be significantly associated with the LV phenotypes. To better understand the association between rs943580 and MVE, we examined AGT haplotype associations with MVE. The single SNP association was driven by a large group of SNPs in high linkage disequilibrium that includes the promoter SNP rs5051.

Key Words: population • genetics • hypertrophy • remodeling • angiotensinogen • haplotypes

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