Association between AKT1 but not AKTIP genetic variants and increased risk for suicidal behavior in bipolar patients.
We tested the hypothesis that the presence of AKT1 and AKTIP polymorphisms, target genes that encode key proteins in the signaling of dopaminergic and serotonergic systems, is associated with suicidal behavior in bipolar patients. The subjects were 273 patients diagnosed with bipolar disorder I or II (age = 41.4 +/- 12.9). TaqMan single-nucleotide polymorphism genotyping assays (AKT1: rs2494731, rs3803304, rs3730358, rs10149779, rs2494746, rs1130214 and rs249878; AKTIP: rs9302648 and rs7189819) were used. We found that the AKT1 marker showed an association with suicide attempts (rs1130214, P < 0.05) and attempted violent attacks (rs2494746, P < 0.05). One out of the seven tested markers of AKT1 attained significant genotype association with violent attempt (rs2494731; P < 0.05). A significant association was detected in the AKT1 haplotype test. We did not observe an association between suicidal behavior and AKTIP variants and also did not find an interaction between AKTIP and AKT1 polymorphisms. In addition, we found that demographic and clinical data are associated with lifetime history of suicide attempts. Our data suggest that demographic and clinical characteristics and AKT1 single markers and haplotypes, but not AKTIP polymorphisms or interactions between AKT1 and AKTIP, are associated with increased risk for suicidal behavior in bipolar patients.
Magno
L A V
LA
Departamento de Saúde Mental, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Miranda
D M
DM
Neves
F S
FS
Pimenta
G J
GJ
Mello
M P
MP
De Marco
L A
LA
Correa
H
H
Romano-Silva
M A
MA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D013405:Suicide / Q000523:psychology*; D013406:Suicide, Attempted / Q000523:psychology
C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D005819:Genetic Markers; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt