Gene by environment interactions: Impact on women’s health

Abstract

There is growing appreciation that a particular gene variant can have quite different effects on the expression of a particular phenotype in persons exposed to varying levels of environmental stress. It has been reported, for example, that among persons exposed to a large number of stressful life events those carrying the short (S) allele of the serotonin transporter promoter polymorphism (5HTTLPR) will have higher levels of depressive symptoms than those homozygous for the long (L) allele, while in those not so exposed depressive symptoms do not vary as a function of genotype. In this chapter I review extensive evidence from research in my laboratory that shows it is important, at least for some gene variants, to consider sex/gender as another factor in addition to environmental factors that can moderate the impact of a given gene variant on expression of phenotypes that can influence the development and course of major diseases. We have shown, for example, in two independent samples that, among men exposed to chronic stress in present day life or childhood, those with the 5HTTLPR LL genotype have increased depressive symptom levels; in contrast, among women exposed to the same stressors, it is those with the SS genotype who have higher depressive symptom levels. In research aiming to identify genetic variants that can be used to identify persons at high risk of developing disease it will be important, therefore, to evaluate not only environmental exposures but also sex/gender as moderators of gene effects on phenotype expression.