Association between FKBP5 Functional Polymorphisms and Completed Suicide

Abstract

Objectives: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide.

Methods: The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls.

Results: A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r2 = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010).

Conclusion: The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide.