title: Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.
abstract: It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. michel.guipponi@hcuge.ch
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Samuel
authors.initials: S
authors.lastname: Deutsch
authors.forename: Karine
authors.initials: K
authors.lastname: Kohler
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: François
authors.initials: F
authors.lastname: Le Gal
authors.forename: Monique
authors.initials: M
authors.lastname: Vessaz
authors.forename: Térèse
authors.initials: T
authors.lastname: Laforge
authors.forename: Brice
authors.initials: B
authors.lastname: Petit
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jollant
authors.forename: Sébastien
authors.initials: S
authors.lastname: Guillaume
authors.forename: Patrick
authors.initials: P
authors.lastname: Baud
authors.forename: Philippe
authors.initials: P
authors.lastname: Courtet
authors.forename: Romano
authors.initials: R
authors.lastname: La Harpe
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016728:Self-Injurious Behavior / Q000235:genetics; D013405:Suicide; D055815:Young Adult; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase