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 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.
Kitsios
Georgios
G
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
Zintzaras
Elias
E
D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006333:Heart Failure / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors