Association of FKBP5 gene haplotypes with completed suicide in the Japanese population.
BACKGROUND
The hypothalamus-pituitary-adrenal (HPA) axis is known to have a role in suicidal behaviors in patients with affective disorders. However, the incomplete overlapping of the genetic factors of suicidal behaviors and the genetic factors of affective disorders suggest that the genes associated with predisposition to suicidal behaviors and affective disorders are different. There is increasing evidence that genes regulating the HPA axis have effects on suicidal behaviors. To test this idea, we examined the association of three HPA axis-related genes (glucocorticoid receptor (NR3C1), mineralocorticoid receptors (NR3C2), and FK506 binding protein 5 (FKBP5)) with suicide.


METHODS
We selected 3 SNPs of the FKBP5 (rs3800373, rs1360780, and rs2395635), 2 SNPs of the NR3C1 (rs6196 and rs10052957), and 3 SNPs of the NR3C2 genes (rs5525, rs5522, and rs2070951) based on their frequency in the Japanese population. Using TaqMan probe assays, we determined these SNPs in 219 completed suicide victims and 228 age- and gender-matched healthy control subjects.


RESULTS
No significant differences in genotypic distribution or allelic frequency of any single SNPs between the completed suicide and control groups were observed. The distributions of TT, TC, and GT haplotypes of the FKBP5 gene (comprised of rs3800373 and rs1360780) between the completed suicide and control groups were significantly different (p<0.05 for each haplotype). The TC haplotype withstood correction for multiple comparisons (corrected p = 0.034).


CONCLUSIONS
Our results suggest that haplotypes in FKBP5 gene are associated with completed suicide. This finding needs to be confirmed using rigorous SNPs selection in a larger sample.
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Irwan
I
Supriyanto
Toru
T
Sasada
Masaaki
M
Fukutake
Migiwa
M
Asano
Yasuhiro
Y
Ueno
Yasushi
Y
Nagasaki
Osamu
O
Shirakawa
Akitoyo
A
Hishimoto
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000523:psychology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013405:Suicide; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5