Depression and coronary heart disease (CHD) are prevalent and often co-occurring disorders. Both have been associated with a dysregulated stress system. As a central element of the stress system, the FKBP5 gene has been shown to be associated with depression. In a prospective design, this study aims to investigate the association of FKBP5 with depressive symptoms in CHD patients. N = 268 hospitalized CHD patients were included. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS-D) at four time points (baseline, and after 1 month, 6 months, and 12 months). The functional FKBP5 single-nucleotide polymorphism (SNP) rs1360780 was selected for genotyping. Linear regression models showed that a higher number of FKBP5 C alleles was associated with more depressive symptoms in CHD patients both at baseline (p = 0.015) and at 12-months follow-up (p = 0.025) after adjustment for confounders. Further analyses revealed that this effect was driven by an interaction of FKBP5 genotype with patients’ prior CHD course. Specifically, only in patients with a prior myocardial infarction or coronary revascularization, more depressive symptoms were associated with a higher number of C alleles (baseline: p = 0.046; 1-month: p = 0.026; 6-months: p = 0.028). Moreover, a higher number of C alleles was significantly related to a greater risk for dyslipidemia (p = .016). Our results point to a relevance of FKBP5 in the association of the two stress-related diseases depression and CHD.

抑郁症和冠心病 (CHD) 是普遍存在且经常同时发生的疾病。两者都与失调的压力系统有关。作为压力系统的核心元素，FKBP5基因已被证明与抑郁症有关。在一项前瞻性设计中，本研究旨在调查FKBP5与 CHD 患者抑郁症状的关系。纳入N  = 268 名住院 CHD 患者。使用医院焦虑和抑郁量表 (HADS-D) 在四个时间点（基线、1 个月、6 个月和 12 个月后）测量抑郁症状。功能性FKBP5选择单核苷酸多态性 (SNP) rs1360780 进行基因分型。线性回归模型显示，在调整混杂因素后，在基线 ( p  = 0.015) 和 12 个月的随访 ( p  = 0.025)时，较高数量的FKBP5 C 等位基因与 CHD 患者更多的抑郁症状相关。进一步的分析表明，这种效应是由FKBP5基因型与患者先前 CHD 病程的相互作用驱动的。具体来说，只有在既往有心肌梗死或冠状动脉血运重建的患者中，更多的抑郁症状与更多的 C 等位基因相关（基线：p  = 0.046；1 个月：p  = 0.026；6 个月：p = 0.028）。此外，较高数量的 C 等位基因与较高的血脂异常风险显着相关 ( p  = .016)。我们的结果表明FKBP5在两种压力相关疾病抑郁症和冠心病的关联中的相关性。