title: Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims.
abstract: Serotonergic signaling abnormalities have been implicated in suicide. Tryptophan hydroxylase (TPH), the rate limiting enzyme of serotonin biosynthesis and the serotonin transporter (SLC6A4), involved in the reuptake of serotonin from the synaptic gap, play major role in serotonergic signaling. In this study, we aimed to compare the levels of expression of these serotonin-related genes between suicide completers and controls and to identify genetic loci involved in their regulation. SLC6A4, TPH1, and TPH2 mRNA levels were measured in the ventral prefrontal cortex (VPFC) of 39 suicide completers and 40 matched controls. To identify the molecular basis of gene expression variation, we performed association studies between cis-acting polymorphisms and SLC6A4, TPH1, and TPH2 transcript levels. Finally, association analyses were carried out between suicide and TPH2 cis-single nucleotide polymorphisms (SNPs) in cohorts of 154 suicide completers and 289 control subjects. Whereas SLC6A4 and TPH1 mRNA expression levels did not differ between suicides and controls, TPH2 levels were found significantly increased (P = 0.003) in suicide completers. We observed that SNP rs10748185 located in the promoter region of TPH2 significantly affect levels of TPH2 mRNA expression. However, we did not find positive association between this eQTL (rs10748185) and suicide. Here, we report the simultaneous analysis of the expression of three serotonin-related genes in the VPFC of suicide victims and controls. This study showed that TPH2 expression levels were increased in the VPFC of suicide victims. Although, we identified a genetic variant that explains variance in TPH2 expression, we did not find evidence associating this cis-regulatory SNP with suicidal behavior.
authors.affiliation: Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Neidhart
authors.forename: Brice
authors.initials: B
authors.lastname: Petit
authors.forename: Monique
authors.initials: M
authors.lastname: Vessaz
authors.forename: Térèse
authors.initials: T
authors.lastname: Laforge
authors.forename: Céline
authors.initials: C
authors.lastname: Relecom
authors.forename: Romano
authors.initials: R
authors.lastname: La Harpe
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005796:Genes; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016728:Self-Injurious Behavior / Q000235:genetics; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013405:Suicide / Q000523:psychology*; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014365:Tryptophan Hydroxylase