The FKBP5-gene in depression and treatment response--an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort.
BACKGROUND
In a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment. There was no association between markers in FKBP5 and disease. The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram.


METHODS
We used clinical data and DNA samples from 1809 outpatients with non-psychotic major depressive disorder (DSM-IV criteria), who received up to 14 weeks of citalopram. A subset of 1523 patients of White non-Hispanic or Black race was matched with 739 control subjects for a case-control analysis. The markers rs1360780 and rs4713916 were genotyped on the Illumina platform. TaqMan-assay was used for marker rs3800373.


RESULTS
In the case-control analysis, marker rs1360780 was significantly associated with disease status in the White non-Hispanic sample after correction for multiple testing. A significant association was also found between rs4713916 and remission. Markers rs1360780 and rs4713916 were in strong linkage disequilibrium in the White non-Hispanic but not in the Black population. There was no significant difference in the number of previous episodes of depression between genotypes at any of the three markers.


CONCLUSIONS
These results indicate that FKBP5 is an important target for further studies of depression and treatment response.
Lekman
Magnus
M
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Laje
Gonzalo
G
Charney
Dennis
D
Rush
A John
AJ
Wilson
Alexander F
AF
Sorant
Alexa J M
AJ
Lipsky
Robert
R
Wisniewski
Stephen R
SR
Manji
Husseini
H
McMahon
Francis J
FJ
Paddock
Silvia
S
D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D044383:Black People / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D015283:Citalopram / Q000627:therapeutic use*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D010555:Personality Inventory; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012008:Recurrence; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics* / Q000523:psychology; D000099159:Tacrolimus Binding Protein 5
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D005819:Genetic Markers; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5