Association of FKBP5 gene haplotypes with completed suicide in the Japanese population

Supriyanto, Irwan; Sasada, Toru; Fukutake, Masaaki; Asano, Masaharu; Ueno, Yoshio; Nagasaki, Yasushi; Sato, Osamu; Hishimoto, Akitoyo

doi:10.1016/j.pnpbp.2010.11.019

Cited by 60 publications

(48 citation statements)

References 50 publications

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“…Although the authors also found an association between the same rs1360780 (T)-rs3800373 (C) haplotype (p = 0.034) and suicide, they failed to detect an association between single polymorphisms and suicide [27] . FKBP5 genetic alterations (rs1360780 TT and rs3800373 CC genotypes) have also been linked with suicide attempts in depressed adolescents [24] and in patients diagnosed with bipolar disorder [21].…”

Section: Discussionmentioning

confidence: 99%

“…Coexisting psychiatric disorders and alcohol dependence were not associated with analyzed genetic markers. Also, the Japanese study was based on a suicide victim group from the general population and it did not indicate a relationship with psychopathology [27]. However, it is important to note that psychiatric disorders might be diagnosed in as high as 90% of suicide victims [34].…”

Section: Discussionmentioning

confidence: 99%

“…Since the association between completed suicide and the FKBP5 rs1360780 (T)-rs3800373 (C) haplotype has been previously reported [27] and hypothesized, the correction for multiple tests was not applied. However, when analyzing the association between functional polymorphisms in FKBP5 and completed suicide, a Bonferroni correction was applied with α = 0.025 (for 2 tests: 2 SNPs).…”

Section: Methodsmentioning

confidence: 99%

“…To the best of our knowledge, only one study has investigated possible associations between the FKBP5 gene and suicide [27]. Although the authors have reported an association between haplotypes of the FKBP5 gene and completed suicide, they did not find any association between single nucleotide polymorphisms and suicide.…”

Section: Introductionmentioning

confidence: 99%

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Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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“…This protein regulates the glucocorticoid receptor by decreasing its capacity to bind glucocorticoids, which hampers the ensuing translocation of the glucocorticoid receptor complex to the nucleus. Certain sequence variants of FKBP5 put individuals at increased risk of depression and post-traumatic stress disorder 62,63 , and of showing suicidal behaviour [64][65][66] or experiencing suicidal events in the course of antidepressant treatment 67,68 ; the link with suicidality is particularly strong for subjects with a history of ELA 69,70 . Interestingly, one study reported that the interaction between the FKBP5 genotype and ELA occurs through decreased methylation affecting functional glucocorticoid response elements located in intron 7 of FKBP5, which results in a downstream increase in FKBP5 expression and glucocorticoid receptor resistance 71 .…”

Section: Box 1 | Biological Embedding Through Dna Methylationmentioning

confidence: 99%

The molecular bases of the suicidal brain

2014

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Suicide ranks among the leading causes of death around the world and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors - such as familial and genetic predisposition, as well as early-life adversity - increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors are associated with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes that are associated with suicidality and discusses some promising avenues for future research.

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The Prospect of FKBP51 as a Drug Target

et al. 2012

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The FK506 binding protein 51 (FKBP51) is best known as an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors. In human genetic association studies, FKBP51 has repeatedly been associated with emotion processing and numerous stress-related affective disorders. It has also been implicated in contributing to the glucocorticoid hyposensitivity observed in New World primates. More recently, several research groups have consistently shown a protective effect of FKBP51 knockout or knockdown on stress endocrinology and stress-coping behavior in animal models of depression and anxiety. The principal druggability of FKBP51 is exemplified by the prototypic FKBP ligands FK506 and rapamycin. Moreover, FKBP51 is highly suited for X-ray co-crystallography, which should facilitate the rational drug design of improved FKBP51 ligands. In summary, FKBP51 has emerged as a promising new drug target for stress-related disorders that should be amenable to drug discovery.

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Association of FKBP5 gene haplotypes with completed suicide in the Japanese population

Cited by 60 publications

References 50 publications

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

The molecular bases of the suicidal brain

The Prospect of FKBP51 as a Drug Target

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