Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder.
Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder.
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DOI：
10.1038/npp.2010.37
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发表时间：
2010-07
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影响因子：
--
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FKBP 5调节皮质醇结合亲和力和糖皮质激素受体的核转位。FKBP5基因座的多态性与抑郁发作复发风险增加和抗抑郁治疗的快速反应相关。最近的一项研究表明，FKBP5基因型调节与儿童期虐待相关的创伤后应激障碍（PTSD）症状的风险。1143名欧洲裔美国人（EAs）和1284名非洲裔美国人（AAs）被招募用于物质依赖遗传学研究，他们也接受了终生PTSD筛查。对FKBP5的4个单核苷酸多态性（SNP）rs3800373、rs9296158、rs1360780和rs9470080进行基因分型。采用Logistic回归分析探讨FKBP5基因多态性与儿童期逆境对PTSD发病风险的交互作用。经过多次测试校正后，童年逆境显着增加了PTSD的风险。FKBP5基因型与疾病的发展无关。在AA中，其中一个SNP rs9470080调节了与儿童虐待相关的PTSD风险。如果没有童年的不良经历，具有该SNP的TT基因型的参与者患PTSD的风险最低，而他们在童年逆境暴露后患PTSD的风险最高。此外，在EAs中，酒精依赖被观察到与儿童不良经历以及FKBP5多态性相互作用，以增加PTSD的风险。本研究进一步证明了FKBP5和儿童期虐待对AA患者PTSD风险的基因×环境效应。需要在其他人群中进行进一步研究。
FKBP5 regulates the cortisol binding affinity and nuclear translocation of the glucocorticoid receptor. Polymorphisms at the FKBP5 locus have been associated with increased recurrence risk of depressive episodes and rapid response to antidepressant treatment. A recent study showed that FKBP5 genotypes moderated the risk of posttraumatic stress disorder (PTSD) symptoms associated with childhood maltreatment. One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of FKBP5 polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD. FKBP5 genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, while they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also FKBP5 polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene × environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations.
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影响因子：
4.1
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