FKBP5基因多态性与重度抑郁症相关，但与双相情感障碍无关。

FKBP5 polymorphism is associated with major depression but not with bipolar disorder.

作者信息

Szczepankiewicz Aleksandra, Leszczyńska-Rodziewicz Anna, Pawlak Joanna, Narozna Beata, Rajewska-Rager Aleksandra, Wilkosc Monika, Zaremba Dorota, Maciukiewicz Malgorzata, Twarowska-Hauser Joanna

机构信息

Laboratory of Psychiatric Genetics, Department of Psychiatry; Poznan University of Medical Sciences, Poznan, Poland; Laboratory of Molecular and Cell Biology, Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland.

Laboratory of Psychiatric Genetics, Department of Psychiatry; Poznan University of Medical Sciences, Poznan, Poland; Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.

出版信息

J Affect Disord. 2014 Aug;164:33-7. doi: 10.1016/j.jad.2014.04.002. Epub 2014 Apr 13.

DOI:10.1016/j.jad.2014.04.002

PMID:24856550

Abstract

BACKGROUND

Altered activity of hypothalamus-pituitary-adrenal glands (HPA) axis in response to stress underlies the pathogenesis of mood disorders such as depression and bipolar disorder. Chaperone proteins regulate sensitivity of glucocorticoid receptor (GR) to steroids. We hypothesized that genetic variants within the FKBP5 - gene encoding co-chaperone protein essential in GR signaling - may influence the susceptibility to major depressive disorder and bipolar disorder.

METHODS

In the study participated 528 bipolar patients, 218 patients with major depressive disorder and 742 subjects from control group. Genotypes for eight FKBP5 polymorphisms (rs1360780, rs755658, rs9470080, rs4713916, rs7748266, rs9296158, rs9394309, rs3800373) were established by TagMan SNP Genotyping Assays (Applied Biosystems). Linkage disequilibrium analysis for FKBP5 gene was done in Haploview. Gene-gene interactions between FKBP5 and NR3C1 polymorphisms (reported previously) were analyzed using the multidimensionality-reduction method (MDR).

RESULTS

We have observed an association between five FKBP5 polymorphisms (rs1360780, rs9470080, rs4713916, rs9296158 and rs9394309) and major depressive disorder (p=0.011; p=0.007, p=0.038; p=0.030; p=0.018, respectively), but not bipolar disorder. In linkage disequilibrium analysis we found that seven FKBP5 polymorphisms build haplotype block (rs3800373, rs755658, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080, respectively). We observed that two haplotype combinations (ACATTGT and CCACTAT) were significantly more frequent in the MDD patients than in controls (p=0.014 and p=0.043). We have not observed such an association for BD patients. We have found that interaction between rs9470080 of FKBP5 and rs6198 of NR3C1 influences MDD risk.

LIMITATIONS

The main limitations of this study include low power and limited sample size of MDD patients.

CONCLUSIONS

Single markers and haplotypes of FKBP5 gene and the interaction with glucocorticoid receptor gene (NR3C1) may influence MDD predisposition.

摘要

背景

下丘脑 - 垂体 - 肾上腺（HPA）轴对应激的反应改变是抑郁症和双相情感障碍等情绪障碍发病机制的基础。伴侣蛋白调节糖皮质激素受体（GR）对类固醇的敏感性。我们假设FKBP5基因（编码GR信号传导中必需的共伴侣蛋白）内的基因变异可能影响重度抑郁症和双相情感障碍的易感性。

方法

528例双相情感障碍患者、218例重度抑郁症患者和742名对照组受试者参与了本研究。通过TaqMan SNP基因分型检测（应用生物系统公司）确定了8个FKBP5多态性位点（rs1360780、rs755658、rs9470080、rs4713916、rs7748266、rs9296158、rs9394309、rs3800373）的基因型。在Haploview中对FKBP5基因进行连锁不平衡分析。使用多维度约简方法（MDR）分析FKBP5与NR3C1多态性（先前报道）之间的基因 - 基因相互作用。

结果

我们观察到5个FKBP5多态性位点（rs1360780、rs9470080、rs4713916、rs9296158和rs9394309）与重度抑郁症相关（p值分别为0.011、0.007、0.038、0.030、0.018），但与双相情感障碍无关。在连锁不平衡分析中，我们发现7个FKBP5多态性位点构成单倍型块（分别为rs3800373、rs755658、rs9296158、rs7748266、rs1360780、rs9394309、rs9470080）。我们观察到两种单倍型组合（ACATTGT和CCACTAT）在重度抑郁症患者中比在对照组中显著更常见（p值分别为0.014和0.043）。在双相情感障碍患者中未观察到这种关联。我们发现FKBP5的rs9470080与NR3C1的rs6198之间的相互作用影响重度抑郁症风险。