ReviewAre we ready for pharmacogenomics in heart failure?
Section snippets
Familial and monogenic forms of dilated cardiomyopathy
Familial forms of dilated cardiomyopathy had long been underestimated until prospective studies were performed. With such an approach, Michels et al. (1992) found that dilated cardiomyopathy was familial in at least 20% of cases (12 of 59 index patients). This was confirmed subsequently for other populations (familial forms, 20–56% of cases, depending on the studies) Keeling et al., 1995, Grünig et al., 1998, Mestroni et al., 1999a, Mestroni et al., 1999b. In addition, while the diagnosis of
Genetic factors for left ventricular dimensions and function in the general population
In the general population, studies performed in monozygotic and dizygotic twins do not suggest a significant genetic component for left ventricular dimensions (except for left ventricular mass), or for systolic function at rest (Bielen et al., 1991). However, some data indicate that during exercise tests, there is a significant genetic component for the increase of end-diastolic left ventricular dimensions, or of fractional shortening and for the maximal oxygen uptake Bielen et al., 1991,
Genetic factors for non-monogenic forms of systolic dysfunction
In idiopathic heart failure, most cases are sporadic and the disease is considered to be multifactorial with a possible genetic component. Some studies were therefore conducted to identify genetic factors involved in such cases. These factors are either susceptibility genes, factors involved in the pathophysiology of the disease and which influence the emergence of the disease, either modifier genes, factors modifying the expressivity of the disease, and which influence the degree or the
Genetic polymorphisms of the metabolism of drugs used in heart failure
The genetic determinants of the metabolism of certain drugs used in cardiology is one predictable cause of variability in their pharmacokinetics and effects. The main genetic polymorphisms of these drugs are polymorphisms of N angiotensin converting enzyme tylation and the cytochrome P-450 isozymes. Genetic polymorphisms are usually characterized by several metabolic phenotypes, two in most cases, which allow a distinction between fast and slow metabolisers (Funck-Brentano, 1991). For a given
Conclusion
Obviously, the genetic approach to heart failure is only starting and published results are preliminary. However, the analysis of the genetic aspects of heart failure appears promising and various DNA banks are currently being set up on national or international bases. Identification of the genetic alterations involved in either familial or non-familial heart failure should unravel the molecular mechanisms that lead from left ventricular dysfunction to overt heart failure, and allow the
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