The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription

• DOI: 10.1038/tp.2015.226
• Publication Date: 2016-03-01T15:34:40Z
• Authors: Z R Donaldson; B le Francois; T L Santos; L M Almli; M Boldrini; F A Champagne; V Arango; J J Mann; C A Stockmeier; H Galfalvy; P R Albert; K J Ressler; R Hen
• Keywords: Adult; Male; Adolescent; Mental Disorders; Brain; Gene Expression; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; Young Adult; Receptor, Serotonin, 5-HT1A; Humans; Original Article; Female; Genetic Predisposition to Disease; Aged; Transcription Factors

Abstract 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 expression of gene ( HTR1A ) through altered binding a number transcription factors. To further explore relationship between mental illness expression, we performed dual epidemiological biological studies. First, genotyped cohort 1412 individuals, randomly split into discovery replication cohorts, to examine five psychiatric outcomes: history hospitalization, attempts, substance or alcohol abuse, current posttraumatic stress disorder (PTSD), depression. We found rs6295G allele is associated increased risk for hospitalization attempts. Overall, exposure either childhood non-childhood trauma resulted all outcomes, but did not observe significant interaction modulating outcomes. conjunction, also investigated potential impact postmortem human brain tissue using relative allelic assays. more mRNA produced from C versus G-allele prefrontal cortex (PFC), midbrain nonpsychiatric control subjects. Further, fetal cortex, rs6295C exhibited as early gestational week 18 humans. Finally, C:G ratio was significantly neutralized PFC subjects major depressive (MDD) who committed compared controls, indicating normal patterns be disrupted MDD/suicide. These data provide putative mechanism underlying association illness. Moreover, our results affect during both development adulthood region-specific manner, acting factor findings critical framework conceptualizing common genetic variant, their health.