Human Genome Epidemiology (HuGE) Review Genetic Variation associated with Ischemic Heart Failure: A HuGE Review and Meta-Analysis

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 sys-tematically 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 poly-morphisms, 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 in-dividual 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 websit