Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan.
Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan.
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部署到伊拉克和阿富汗的美国军人中 FKBP5 与 PTSD 的基因关联。
DOI：
10.1016/j.jpsychires.2019.12.014
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发表时间：
2020
影响因子：
4.8
通讯作者：
Ursano,RobertJ
中科院分区：
文献类型：
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作者：
Zhang,Lei;Hu,Xian-Zhang;Yu,Tianzheng;Chen,Ze;Dohl,Jacob;Li,Xiaoxia;Benedek,DavidM;Fullerton,CarolS;Wynn,Gary;Barrett,JamesE;Li,Mian;Russell,DaleW;Biomarkerteam;Ursano,RobertJ
创伤后应激障碍（PTSD）是一种使人衰弱的精神障碍，在美国人口中的患病率超过7%，在军队中的患病率为12%。据报道，儿童创伤与FKBP 5（糖皮质激素调节的亲免疫素）的相互作用与一般人群中的PTSD有关。然而，关于FKBP 5与PTSD相关性的报道很少，特别是在重要的高危人群如军人中。在这里，我们检查了覆盖FKBP 5基因的四种单核苷酸多态性（SNP; rs3800373、rs 9296158、rs 1360780、rs 9470080）与部署到伊拉克和阿富汗的美国服役人员（高风险军事群体，n = 3890）中可能的PTSD之间的关联（Hines et al.，2014）。我们发现可能的PTSD受试者更可能携带rs3800373的A等位基因，rs 9296158的G等位基因，rs 1360780的C等位基因和rs 9470080的C等位基因。此外，4个SNPs处于一个强成对连锁不平衡区（r = 0.91-0.96）。在该区块内，存在两种主要的单倍型CATT和AGCC（rs3800373-rs 9296158-rs 1360780-rs 9470080），其占单倍型多样性的99%。与非PTSD受试者相比，AGCC单倍型在可能的PTSD受试者中的分布显著更高（p<0.05）。基于双体型的分析表明，AGCC携带者倾向于可能的PTSD。在这项研究中，我们证明了FKBP 5与部署到伊拉克和阿富汗的美国服务人员可能的PTSD之间的关联，表明FKBP 5可能是PTSD的风险因素。
Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with a prevalence of more than 7% in the US population and 12% in the military. An interaction of childhood trauma with FKBP5 (a glucocorticoid-regulated immunophilin) has been reported to be associated with PTSD in the general population. However, there are few reports on the association of FKBP5 with PTSD, particularly in important high-risk population such as the military. Here, we examined the association between four single-nucleotide polymorphisms (SNPs; rs3800373, rs9296158, rs1360780, rs9470080) covering the FKBP5 gene and probable PTSD in US service members deployed to Iraq and Afghanistan, a high-risk military population (n = 3890) (Hines et al., 2014). We found that probable PTSD subjects were significantly more likely to carry the A-allele of rs3800373, G-allele of rs9296158, C-allele of rs1360780, and C-allele of rs9470080. Furthermore, the four SNPs were in one block of strong pairwise linkage disequilibrium (r = 0.91–0.96). Within the block there were two major haplotypes of CATT and AGCC (rs3800373-rs9296158-rs1360780-rs9470080) that account for 99% of haplotype diversity. The distribution of the AGCC haplotype was significantly higher in probable PTSD subjects compared to non-PTSD (p<.05). The diplotype-based analysis indicated that the AGCC carriers tended to be probable PTSD. In this study, we demonstrated the association between FKBP5 and probable PTSD in US service members deployed to Iraq and Afghanistan, indicating that FKBP5 might be a risk factor for PTSD.