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A new approach for the identification of modifier genes in heart failure

The Pharmacogenomics Journal volume 4, pages 221–223 (2004)Cite this article

The identification of genetic factors involved in a multifactorial disease such as heart failure is a complex challenge which may benefit from multiple and complementary approaches.1, 2, 3

The strategy widely used until now in humans is based on association studies between the disease and polymorphisms in candidate genes.4, 5, 6 The choice of the genes of interest is based on the biological plausibility of their involvement in the pathophysiology of the disease. This strategy has already led to the identification of susceptibility genes (involved in the genesis of the disease) or modifier genes (which may modulate the severity of the disease once it has developed) involved in heart failure of idiopathic cause (dilated cardiomyopathy) or of ischaemic origin.4, 5, 6 Some of these polymorphisms are located in genes encoding adrenoreceptors or renin–angiotensin–aldosterone peptides. However, most results of available studies still cannot be considered as definitive because of the small size of the populations, the lack of replication and ethnic stratification. The statistical power is limited since parameters other than genetic background largely contribute to the phenotypic variability (etiology, treatment, environment…). This low statistical power prevents the analysis of gene–gene and gene–environment interactions, which are likely to play a major role in this multifactorial disease. A final limitation is that the selection of candidate genes is obviously limited by our knowledge of the pathophysiology of heart failure.

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Authors and Affiliations

  1. Département de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France

    M Komajda & P Charron

  2. INSERM U621, Hôpital Pitié-Salpêtrière, Paris, France

    M Komajda & P Charron

  3. Département de Génétique, Hôpital Pitié-Salpêtrière, Paris, France

    P Charron

Authors
  1. M Komajda
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  2. P Charron
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Correspondence to M Komajda.

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None declared.

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Komajda, M., Charron, P. A new approach for the identification of modifier genes in heart failure. Pharmacogenomics J 4, 221–223 (2004). https://doi.org/10.1038/sj.tpj.6500257

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