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American Journal of Epidemiology Advance Access originally published online on July 21, 2007
American Journal of Epidemiology 2007 166(6):619-633; doi:10.1093/aje/kwm129
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Genetic Variation associated with Ischemic Heart Failure: A HuGE Review and Meta-Analysis

Georgios Kitsios1 and Elias Zintzaras1,2

1 Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece
2 Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA

Correspondence to Prof. Elias Zintzaras, Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, 750 Washington Street, Tufts-NEMC #63, Boston, MA 02111 (e-mail: ezintzaras{at}tufts-nemc.org).

Received for publication January 24, 2007. Accepted for publication March 21, 2007.

The ischemic etiology of heart failure is an independent prognostic factor associated with worse long-term outcome. Recent evidence indicates a role for genetic susceptibility to ischemic heart failure. The authors systematically reviewed all known case-control studies that investigated the association between genetic variants and ischemic heart failure. Twenty-two articles, which examined 24 gene polymorphisms, were identified. In 22 polymorphisms, the variant form had a functional effect. Twenty-two polymorphisms were variants of genes involved in the maladaptive neurohormonal activation. Seven polymorphisms (ACE I/D, AGT M235T, ADRA2C Del322-325, ADRB2 Arg16Gly, ADRB2 Gln27Glu, EDN1 Lys198Asn, VEGF G-405C) showed a significant association in individual studies. Five polymorphisms (ACE I/D, ADRB1 Arg389Gly, ADRB2 Arg16Gly, ADRB2 Gln27Glu, TNF G308A) were examined by more than one study, and meta-analyses were performed. The meta-analyses showed no significant sign of heterogeneity. In all settings, there was no significant association, except for polymorphism ADRB2 Arg16Gly under a recessive model (fixed-effects odds ratio = 1.32, 95% confidence interval: 1.05, 1.65). Taking into account that ischemic heart failure is a complex disease with multifactorial etiology, a minor contributing pathogenetic role of the investigated gene polymorphisms cannot be totally excluded. Case-control studies that investigate gene-gene and gene-environment interactions might further elucidate the genetics of ischemic heart failure.

epidemiology; heart failure, congestive; meta-analysis; myocardial ischemia; polymorphism, genetic; variation (genetics)

Abbreviations: CI, confidence interval; HWE, Hardy-Weinberg equilibrium; IHF, ischemic heart failure; SNP, single nucleotide polymorphism

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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