Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort.
BACKGROUND
Genetic variations in FKBP5, BDNF, P2RX7 and CACNA1 are current candidates for involvement in depression.


METHODS
The single nucleotide polymorphisms FKBP5:rs1360780, BDNF:rs6265 (Val66Met), P2RX7:2230912 (Gln460Arg) and CACNA1C:rs1006737 were genotyped in DNA from 457 depression cases (major depression, dysthymia, and mixed anxiety depression) and 2286 healthy controls with no symptom of psychopathology. Cases and controls were derived from a large well-characterized longitudinal population-based sample of adult Swedes with data on life situation and life history. Association to depression was analyzed with and without consideration to problems during childhood and negative life events last year.


RESULTS
FKBP5:rs1360780 allele T and genotype TT were overrepresented in depression for men. Childhood problems and negative life events (two or more) conferred a risk for depression (OR=2.8, 95% CI: 2.2-3.5 and OR=2.9, 95% CI: 2.4-3.7, respectively). The BDNF:rs6265 Met-allele was overrepresented in depression for women with problems during their childhood. No indication for association to depression was found for P2RX7:2230912 and CACNA1C:rs1006737 without or with consideration of childhood problems or negative life events.


CONCLUSIONS
The sample size did not allow exclusion of true association to depression at low odds ratios. There was possibly some recall bias of childhood problems.


CONCLUSIONS
These data support previous reports on FKBP5:rs1360780 and show a gender difference. Likewise, they support previous reports on BDNF:rs6265 and show involvement of environmental stress. P2RX7:2230912 and CACNA1C:rs1006737 did not have a large or moderate-size effect on depression risk. Further studies are required to estimate the significance of these findings.
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden. catharina.lavebratt@ki.se
Catharina
C
Lavebratt
Elin
E
Aberg
Louise K
LK
Sjöholm
Yvonne
Y
Forsell
D000328:Adult; D000483:Alleles; D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D019263:Dysthymic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
D019208:Brain-Derived Neurotrophic Factor; D020746:Calcium Channels, L-Type; D058486:Receptors, Purinergic P2X7; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C079146:CACNA1C protein, human; C546468:P2RX7 protein, human