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KMID : 0605720140200010035
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Journal of the Korean Society of Biological Therapies in Psychiatry
2014 Volume.20 No. 1 p.35 ~ p.44
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Gene Environment Interaction and Epigenetic Modulation of FKBP5 in Childhood Trauma
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Joo Yeol
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Abstract
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It is well known that trauma during childhood significantly increases risk for posttraumatic stress disorder(PTSD), other mood and anxiety disorder in adulthood. Childhood trauma is known as altered regulations of the HPA axis in adulthood. Considering the importance of the HPA system in the etiology of PTSD, the effect of childhhood trauma on adult with PTSD and other psychiatric disorders may be mediated by dysregulation of the HPA axis. Recently, it has been recognized that for the development of PTSD, complex interplay between genetic predisposition and environmental factors plays crucial roles. FKBP5, which is a HSP90-associated co-chaperone, regulates sensitivity of glucocorticoid receptor. Multiple studies replicated the findings that interaction of FKBP5 genetic variants and childhood trauma significantly increased the risk of adult PTSD, suicide attempt and aggressive behaviour. Recent studies suggest that in specific risk allele of FKBP5 single nucleotide polymorphism(SNP), 3D conformational change of intron increases the expression of FKBP5 in response to stress. In addition, the model which explains the difference of epigenetic modulation of FKBP5 between risk allele and protective allele has been proposed. The findings that in FKBP5 SNP risk allele, relative irreversibility of cytosine demethylation by environmental factor occurs only in developmentally vulnerable period, may shed light on molecular underpinnings of long lasting effect of childhood trauma.
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KEYWORD
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Childhood trauma, Posttraumatic stress disorder, FKBP5, Gene-environment interaction, Epigenetic regulation
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