Introduction: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression. Methods: Genotyping for the two variants within the FKBP5 gene was performed using PCR-restriction fragment length polymorphism and Taqman® real-time PCR in a cohort of 179 inpatients who were monitored for the first 3 weeks of antidepressant drug treatment. The early response to antidepressant drugs was assessed as percentage of decline in Hamilton depression score after 3 weeks, responders versus nonresponders were distinguished by a 50% decrease. Results: The FKBP5 variants rs3800373 and rs1360780 were highly linked, and carriers of the FKBP5 variants had a trend towards a higher chance to respond (p = 0.04; odds ratio: 1.8; 95% Cl: 0.98-3.3). When analyzing drug-specific subgroups, the effect was seen mainly in the subgroups of patients treated with antidepressant drug combinations or with venlafaxine. Conclusion: In this study, an effect of FKBP5 variants on antidepressant drug response was confirmed in an independent cohort of depressed patients; however, with an odds ratio of 1.8 the effect size was smaller than that described earlier. © 2008 Future Medicine Ltd.
CITATION STYLE
Kirchheiner, J., Lorch, R., Lebedeva, E., Seeringer, A., Roots, I., Sasse, J., & Brockmöller, J. (2008). Genetic variants in FKBP5 affecting response to antidepressant drug treatment. Pharmacogenomics, 9(7), 841–846. https://doi.org/10.2217/14622416.9.7.841
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