Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease.

Abstract

There is now considerable evidence that elements of the heritable or familial component of disease susceptibility are transmitted by nongenomic means, and that environmental influences acting during early development shape disease risk in later life. The underlying mechanisms are thought to involve epigenetic modifications in nonimprinted genes induced by aspects of the developmental environment, which modify gene expression without altering DNA sequences. These changes result in life-long alterations in gene expression. Such nongenomic tuning of phenotype through developmental plasticity has adaptive value because it attempts to match an individual's responses to the environment predicted to be experienced. When the responses are mismatched, disease risk increases. An example of such mismatch is that arising either from inaccurate nutritional cues from the mother or placenta before birth, or from rapid environmental change through improved socioeconomic conditions, which contribute substantially to the increasing prevalence of type-2 diabetes, obesity, and cardiovascular disease. Recent evidence suggests that the effects can be transmitted to more than the immediately succeeding generation, through female and perhaps male lines. Future research into epigenetic processes may permit us to develop intervention strategies.