Contribution of adenosine related genes to the risk of depression with disturbed sleep

Background: Most patients with major depression report problems in their sleep: insomnia, early morning awakenings and fatigue correlating with poor sleep quality. One of the key substances regulating sleep is adenosine. We hypothesized that variations in polymorphic sites of adenosine related genes may predispose to depression with sleep disturbances. Methods: We selected 117 single nucleotide polymorphisms from 13 genes and analyzed their association with depression and specific sleep problems (early morning awakenings and fatigue). Data were collected as part of the Health 2000 Study based on Finnish population and included 1423 adult subjects. Results: Our major finding herein was, among women, the association of SLC29A3 polymorphism rs12256138 with depressive disorder (p = 0.0004, odds ratio = 0.68, 95% CI 0.55-0.84, p < 0.05 after Bonferonni correction for multiple testing). Only one gene showing any evidence for association was common to women and men (ADA). Limitations: Relatively small size of the case samples. Conclusions: Our results suggest that compromised adenosine transport due to variation in nucleoside transporter gene SLC29A3 in women, could predispose to depression, and could suggest new directions in treatment research. The shortage of overlapping genes between the genders indicates that the genetics of mood regulation may vary between the sexes.