Gene–environment interaction and its impact on coronary heart disease risk

Coronary heart disease (CHD) is a major cause of mortality in the western world, and is known to be modified by both genetic and environmental factors. This suggests that at the molecular level there is interaction between the gene product(s) and/or the by-products of the environmental insult, and from a statistical viewpoint this implies a deviation from the expected multiplicative effect on risk. In other words genetic risk is modifiable in an environment-specific manner. This Review focuses on recently reported effects of smoking and alcohol (environmental factors) on the impact of variation in the genes for apoE (APOE) and alcohol dehydrogenase (ADHC1) on heart disease risk. Considering gene–environment interaction has the potential not only for improving our understanding of the pathophysiology of the disease, but also in the development and targeting of specific therapies.