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(Hypertension. 2008;51:778.)
© 2008 American Heart Association, Inc.

Original Articles

Meta-Analysis of the Association of 4 Angiotensinogen Polymorphisms With Essential Hypertension

A Role Beyond M235T?

Tiago Veiga Pereira; Ane C.F. Nunes; Martina Rudnicki; Yoshiji Yamada; Alexandre Costa Pereira; José E. Krieger

From the Heart Institute (InCor) (T.V.P., A.C.P., J.E.K.) and Clinical and Toxicological Analysis Department (M.R.), Faculty of Pharmaceutical Sciences, University of Sao Paulo Medical School, São Paulo, Brazil; Division of Nephrology (A.C.F.N.), São Paulo University Medical School, University of São Paulo, São Paulo, Brazil; and the Department of Human Functional Genomics (Y.Y.), Life Science Research Center, Mie University, Mie, Japan.

Correspondence to José E. Krieger, InCor, Laboratório de Genética e Cardiologia Molecular/LIM 13, Av Dr Enéas Carvalho Aguiar, 44, São Paulo–SP, CEP-05403-000, Brazil. E-mail krieger{at}incor.usp.br

Angiotensinogen (AGT) gene polymorphisms have been linked to increased risk of hypertension, but the data remain controversial. In this study we review the most commonly investigated polymorphisms at the AGT locus (other than M235T) and provide summary estimates regarding their association with essential hypertension, while addressing heterogeneity, as well as publication biases. Data on 26 818 subjects from 46 studies for the 4 most-studied AGT variants (T174M in exon 2 and 3 promoter variants: A-6G, A-20C, and G-217A) were meta-analyzed. Statistically significant associations with hypertension were identified for the T174M (odds ratio [OR]: 1.19; 95% CI: 1.07 to 1.33; P=0.002) and G-217A (OR: 1.37; 95% CI: 1.17 to 1.59; P=0.00006) polymorphisms. A dual but consistent effect was observed for the –20C allele, which was associated with a decreased risk of hypertension in populations of mixed and European ancestries (OR: 0.64; 95% CI: 0.44 to 0.92; P=0.02 and OR: 0.77; 95% CI: 0.65 to 0.91; P=0.003, respectively), but with a 24% increase in the odds of hypertension in Asian subjects (OR: 1.24; 95% CI: 1.04 to 1.48; P=0.02). No association of the A-6G variant with hypertension was detected. Current studies support the notion that single variants at the AGT might modulate the risk of hypertension but indicate caution in interpreting these results because of the putative presence of publication bias and gene-environment interactions.

Key Words: angiotensinogen • hypertension • polymorphism • meta-analysis • T174M • M235T