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Association of FK506 binding protein 5 (FKBP5) gene rs4713916 polymorphism with mood disorders: a meta-analysis

  • Xiao-Liang Feng (a1), Fang Wang (a2), Yan-Feng Zou (a1), Wen-Fei Li (a3), Yang-Hua Tian (a4), Fa-Ming Pan (a1) and Fen Huang (a1)...


Background: Several studies have investigated the association of FKBP5 gene polymorphisms with mood disorders, but findings are not always consistent. The aim of our study was to assess the association of FKBP5 gene polymorphisms with mood disorders using a meta-analysis.

Methods: Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang, with the last report up to March 2010. Meta-analysis was performed in a fixed/random effect model.

Results: We identified six studies using search, and one study was excluded because of unavailable data. One study contained data on two different ethnicities and we treated them independently. Thus, six separate studies (2655 cases and 3593 controls) were included in the meta-analysis. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373 and rs4713916) in overall and Caucasian populations. We did not detect any association of FKBP5 gene rs1360780 and rs3800373 polymorphisms with mood disorders (p > 0.05). However, a significant association of FKBP5 gene rs4713916 polymorphism with mood disorders was found, and the heterozygous individual (GA genotype) was more susceptible to mood disorders in comparison to homozygous analogues (GG or AA genotype) [overall: GA vs. GG: OR (odds ratio) = 1.20, 95% CI (confidence interval) = 1.03–1.40, p = 0.02; GA vs. AA: OR = 1.44, 95% CI = 1.09–1.90, p = 0.009; Caucasian: GA vs. GG: OR = 1.22, 95% CI = 1.04–1.44, p = 0.01; GA vs. AA: OR = 1.43, 95% CI = 1.09–1.89, p = 0.01].

Conclusion: This meta-analysis shows that mood disorders are associated with FKBP5 gene rs4713916 polymorphism, but not with rs1360780 and rs3800373.


Corresponding author

Yan-Feng Zou, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China. Tel: +86 105513869140; Fax: +86 105513869140; E-mail:


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1.Lee, S, Jeong, J, Kwak, Y, Park, SK.Depression research: where are we now? Mol Brain 2010;3:8.
2.Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE.Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593602.
3.Greenberg, PE, Stiglin, LE, Finkelstein, SN, Berndt, ER.The economic burden of depression in 1990. J Clin Psychiatry 1993;54:405418.
4.Sartorius, N.The economic and social burden of depression. J Clin Psychiatry 2001;62:811.
5.Wittchen, HU, Jacobi, F.Size and burden of mental disorders in Europe – a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005;15:357376.
6.Fan, M, Liu, B, Jiang, T, Jiang, X, Zhao, H, Zhang, J.Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders. Psychiatr Genet 2010; 20:17.
7.Beckman, G, Beckman, L, Cedergren, B, Perris, C, Strandman, E.Serum protein and red cell enzyme polymorphisms in affective disorders. Hum Hered 1978;28: 4147.
8.Lopez-Leon, S, Janssens, AC, Gonzalez-Zuloeta Ladd, AM et al. Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 2008;13:772785.
9.Holsboer, F.The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res 1999;33:181214.
10.Holsboer, F.The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000;23:477501.
11.Nair, SC, Rimerman, RA, Toran, EJ et al. Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor. Mol Cell Biol 1997;17:594603.
12.Cheng, R, Juo, SH, Loth, JE et al. Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry 2006;11:252260.
13.Binder, EB.The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 2009;34:S186S195.
14.Binder, EB, Salyakina, D, Lichtner, P et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004;36:13191325.
15.Binder, EB, Bradley, RG, Liu, W et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008;299:12911305.
16.Zobel, A, Schuhmacher, A, Jessen, F et al. DNA sequence variants of the FKBP5 gene are associated with unipolar depression. Int J Neuropsychopharmacol 2010;13:649660.
17.Lavebratt, C, Aberg, E, Sjoholm, LK, Forsell, Y.Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort. J Affect Disord 2010;125:249255.
18.Lekman, M, Laje, G, Charney, D et al. The FKBP5-gene in depression and treatment response–an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry 2008;63: 11031110.
19.Papiol, S, Arias, B, Gasto, C, Gutierrez, B, Catalan, R, Fananas, L.Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. J Affect Disord 2007;104:8390.
20.Gawlik, M, Moller-Ehrlich, K, Mende, M et al. Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits. BMC Psychiatry 2006;6:52.
21.Munafo, MR, Flint, J.Meta-analysis of genetic association studies. Trends Genet 2004;20:439444.
22.Cochran, WG.The combination of estimates from different experiments. Biometrics 1954;10:101129.
23.Higgins, JP, Thompson, SG.Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:15391558.
24.Mantel, N, Haenszel, W.Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719748.
25.Dersimonian, R, Laird, N.Meta-analysis in clinical trials. Control Clin Trials 1986;7:177188.
26.Egger, M, Davey, SG, Schneider, M, Minder, C.Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997;315:629634.
27.Willour, VL, Chen, H, Toolan, J et al. Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 2009;14:261268.
28.Sarginson, JE, Lazzeroni, LC, Ryan, HS, Schatzberg, AF, Murphy, GJ.FKBP5 polymorphisms and antidepressant response in geriatric depression. Am J Med Genet B Neuropsychiatr Genet 2010;153B:554560.
29.Horstmann, S, Lucae, S, Menke, A et al. Polymorphisms in GRIK4, HTR2A, and FKBP5 show interactive effects in predicting remission to antidepressant treatment. Neuropsychopharmacology 2010;35:727740.
30.Kirchheiner, J, Lorch, R, Lebedeva, E et al. Genetic variants in FKBP5 affecting response to antidepressant drug treatment. Pharmacogenomics 2008;9:841846.
31.Tsai, SJ, Hong, CJ, Chen, TJ, Yu, YW.Lack of supporting evidence for a genetic association of the FKBP5 polymorphism and response to antidepressant treatment. Am J Med Genet B Neuropsychiatr Genet 2007;144B:10971098.
32.Brent, D, Melhem, N, Ferrell, R et al. Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry 2010;167:190197.
33.Binder, EB, Lucae, S, Salyakina, D et al. SNPs in FKBP5 determine a novel subtype of depression characterized by rapid response to antidepressant treatment. Eur Neuropsychopharmacol 2006;16(Suppl. 1):S75.
34.Grad, I, Picard, D.The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol 2007;275: 212.
35.Pace, TW, Miller, AH.Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann N Y Acad Sci 2009;1179:86105.
36.Maes, M, Galecki, P, Chang, YS, Berk, M.A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2010. [Epub ahead of print]
37.Ioannidis, JP, Ntzani, EE, Trikalinos, TA, Contopoulos-Ioannidis, DG.Replication validity of genetic association studies. Nat Genet 2001;29:306309.



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