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Proc Nutr Soc. 2002 Nov;61(4):457-63.

Gene-environment interaction: a central concept in multifactorial diseases.

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Institut National de la Santé et de la Recherche Médicale U525, Faculté de Médecine Pitié-Salpétrière, 91 Bd de l'Hôpital, 75634 Paris Cedex, France.


Unlike the rare and severe genetic defects that cause monogenic diseases, the genetic factors that modulate the individual susceptibility to multifactorial diseases (cardiovascular diseases, cancers, diabetes, etc.) are common, functionally different, forms of genes (polymorphisms), which generally have a modest effect at an individual level but, because of their high frequency in the population, can be associated with a high attributable risk. Environmental factors can reveal or facilitate the phenotypic expression of such susceptibility genes. Indeed, in common diseases genetic effects can be considerably amplified in the presence of triggering factors. There is now accumulating evidence that most of the susceptibility genes for common diseases do not have a primary aetiological role in predisposition to disease, but rather act as response modifiers to exogenous factors such as stress, environment, disease, drug intake. A better characterisation of the interactions between environmental and genetic factors constitute a key issue in the understanding of the pathogenesis of multifactorial diseases. The present paper will review three examples of gene-environment interactions in the field of CHD.

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