Modifier genes and heart failure.

Journal Article (Review)

Recent progress in genomic applications have led to a better understanding of the relationship between genetic background and cardiovascular diseases such as heart failure. A considerable component of the variability in heart failure outcome is due to modifier genes, i.e. genes that are not involve in the genesis of a disease but modify the severity of the phenotypic expression once the disease has developed. The strategy most commonly used to identify modifier genes is based on association studies between the severity of the phenotype of the disease (morbidity and/or mortality) and the sequence variation(s) of selected candidate gene(s). This strategy has showed that several polymorphisms of the beta1 and beta2 adrenergic receptors genes and the angiotensin converting enzyme gene are correlated to the prognosis of patients with heart failure. Recently, we have applied an experimental strategy, known as genome mapping, for the identification of heart failure modifier genes. Genome mapping has previously been used with success to identify the genes involved in the development of both monogenic and multifactorial diseases. We have showed that the prognosis of heart failure mice, induced through overexpressing calsequestrin, is linked to 2 Quantitative Trait Loci (QTL) localized on chromosome 2 and 3. Using both strategies (candidate gene and genome mapping) should allow us to identify a number of modifier genes that may provide a more rational approach to identify patients at risk for disease and response to therapy.

Full Text

Duke Authors

Cited Authors

  • Le Corvoisier, P; Park, HY; Rockman, HA

Published Date

  • April 2003

Published In

Volume / Issue

  • 51 / 2

Start / End Page

  • 107 - 120

PubMed ID

  • 12783067

International Standard Serial Number (ISSN)

  • 0026-4725

Language

  • eng

Conference Location

  • Italy