The G/C single-nucleotide polymorphism in the serotonin 1a receptor promoter, rs6295, has previously been linked with depression, suicide and antidepressant responsiveness. In vitro studies suggest that rs6295 may have functional effects on the expression of the serotonin 1a receptor gene through altered binding of a number of transcription factors.
In this study, the rs6295G allele is reported to be associated with increased risk for substance abuse, psychiatric hospitalization and suicide attempts. Overall, exposure to either childhood or non-childhood trauma resulted in increased risk for all psychiatric outcomes, but there was no significant interaction between rs6295 and trauma in modulating psychiatric outcomes.
The authors also investigated the potential impact of rs6295 on 5-HT1A receptor expression in postmortem human brain tissue using relative allelic expression assays. Their results suggest that rs6295 may affect transcription during both gestational development and adulthood in a region-specific manner, acting as a risk factor for psychiatric illness.
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Donaldson ZR, le Francois B, Santos TL, almli LM, Boldrini M, Champagne FA, Arango V, Mann JJ, Stockmeier CA, Galfalvy H, Albert PR, Ressler KJ and Hen R: The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription. Transl. Psychiatry 2016 Mar 1;6:e746. doi: 10.1038/tp.2015.226.
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