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FKBP5 多态性与肾移植受者抑郁症状的关系。

Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients.

机构信息

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota 55905, USA.

出版信息

Depress Anxiety. 2011 Dec 21;28(12):1111-8. doi: 10.1002/da.20879. Epub 2011 Aug 24.

Abstract

BACKGROUND

Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a history of child abuse have been shown to be associated with an increased risk for posttraumatic stress disorder (PTSD). It has also been demonstrated that the same polymorphisms of FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. However, there are only limited numbers of studies replicating the polymorphisms as vulnerability factors for the development of mental illnesses, such as PTSD and depression after stressful life event, especially with a specific incidence, such as kidney transplant surgery.

METHODS

A retrospective analysis was conducted using the electronic medical records of 131 adult kidney transplant recipients. Depression severity after kidney transplantation was measured by PHQ-9, and stored blood was genotyped for variants in the Serotonin Transporter (SLC6A4), Brain-Derived Neurotrophic Factor, Catecholamine-O-Methyltransferase, Corticotropin-Releasing Hormone Receptor, and FKBP5 genes. Spearman correlations were used to test for association between genetic variants and depression severity.

RESULTS

The rare alleles at three out of four SNPs in FKBP5 (rs1360780, rs9296158, and rs9470080) were associated with increased PHQ-9 scores (P<.05), whereas the last FKBP5 SNP (rs3800373) showed a trend of association (P<.10). All four FKBP5 SNPs are in strong linkage disequilibrium. Although in a subgroup of Caucasian non-Hispanic subjects the association was not statistically significant, the direction of association was consistent with that observed in the entire sample as well as in previous studies. Polymorphisms in genes other than FKBP5 were not associated with PHQ-9 scores.

CONCLUSIONS

Polymorphisms in FKBP5 may be associated with higher depression scores in kidney transplant recipients.

摘要

背景

FK506 结合蛋白基因(FKBP5)的几种多态性和儿童虐待史已被证明与创伤后应激障碍(PTSD)的风险增加有关。已经证明,FKBP5 的相同多态性与抑郁发作的复发增加和对抗抑郁治疗的快速反应有关。然而,只有有限数量的研究复制了 FKBP5 的多态性作为易患因素,例如 PTSD 和应激性生活事件后的抑郁症,特别是具有特定发生率的疾病,例如肾移植手术。

方法

使用 131 名成年肾移植受者的电子病历进行回顾性分析。肾移植后抑郁严重程度采用 PHQ-9 进行测量,并对 5-羟色胺转运体(SLC6A4)、脑源性神经营养因子、儿茶酚-O-甲基转移酶、促肾上腺皮质激素释放激素受体和 FKBP5 基因中的变体进行存储血液基因分型。Spearman 相关性用于测试遗传变异与抑郁严重程度之间的关联。

结果

FKBP5 中四个 SNP 中的三个罕见等位基因(rs1360780、rs9296158 和 rs9470080)与 PHQ-9 评分增加相关(P<.05),而最后一个 FKBP5 SNP(rs3800373)显示出关联的趋势(P<.10)。所有四个 FKBP5 SNP 均处于强连锁不平衡状态。虽然在白种非西班牙裔亚组中,关联没有统计学意义,但关联的方向与整个样本以及先前研究一致。除 FKBP5 以外的基因的多态性与 PHQ-9 评分无关。

结论

FKBP5 的多态性可能与肾移植受者的抑郁评分较高有关。

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