Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.
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.
Guipponi
Michel
M
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. michel.guipponi@hcuge.ch
Deutsch
Samuel
S
Kohler
Karine
K
Perroud
Nader
N
Le Gal
François
F
Vessaz
Monique
M
Laforge
Térèse
T
Petit
Brice
B
Jollant
Fabrice
F
Guillaume
Sébastien
S
Baud
Patrick
P
Courtet
Philippe
P
La Harpe
Romano
R
Malafosse
Alain
A
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
D000123:Acetyltransferases; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase