The 3111T/C Polymorphism Interacts With Stressful Life Events to Influence Patterns of Sleep in Females

Abstract

Genetic variations in clock-relevant genes have been investigated in relation to sleep abnormalities, both in healthy populations and in mood-disorder patients with inconsistent results. Environmental influences may moderate associations between genes and phenotype. The authors examined the CLOCK 3111T/C polymorphism and several variants within the PER3 gene and their possible interaction with stressful life events in a group of female volunteers (n = 415). Gene-environment (G × E) interactions and gene main effects were investigated on depressive symptoms using the Beck Depression Inventory and on change of sleep patterns (Item 16). Results showed a G × E interaction on alteration of sleeping pattern: the 3111C homozygous genotype reported greater disruption in sleep pattern after the experience of stressful life events. Within the PER3 gene, one G × E interaction was observed with rs228642 on sleep change. These findings show that the 3111T/C polymorphism is not associated with depressive symptoms, but only with symptoms of sleep change in the case of prior stressful life experiences. The combination of a sensitive genotype (3111C/C) and environmental stress increases vulnerability to circadian rhythm disruption in females. (Author correspondence: [email protected])

Keywords:

• CLOCK gene
• Depression
• Human beings
• PER3 gene
• Sleep
• Stress

ACKNOWLEDGMENTS

We would like to thank the Prefect of Xanthi, G. Pavlidis; the Health Director of the Prefecture of Xanthi, A. Nearchou; and S. Vitoratou from the University Mental Health Research Institute in Athens, Greece, for their valuable assistance.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was funded by the grant: “INTERREG IIIA/PHARE CBC Greece Bulgaria: Actions taken for the mental health of women of mountainous Xanthi.” The work of Niki Antypa is supported by the “Rubicon” Grant, awarded by the Netherlands Organization of Scientific Research (NWO) to the author. The funding bodies had no involvement in the research.