Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

Abstract

The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1-3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined.

Figure 1

Circadian Clock. Positive regulation of clock genes Bmal1 and Clock stimulates promoter of negative regulators Per1–3, Cry 1-2, and controlled clock genes StAR, 3β-HSD, DBP, VEGF, Hexokinase, and Wee-1. Moreover, the molecular clock regulates the deacetylase activity of SIRT1 by regulation of NAD⁺/NADH ratio.