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脑源性神经营养因子基因多态性与冠状动脉疾病相关的抑郁及抗抑郁反应有关。

Brain‑derived neurotrophic factor gene polymorphisms are associated with coronary artery disease‑related depression and antidepressant response.

作者信息

Liu Yong-Qiang, Su Guo-Bao, Duan Chang-Hong, Wang Jun-Hua, Liu Hai-Mei, Feng Nan, Wang Qing-Xi, Liu Xu-En, Zhang Jie

机构信息

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.

The Third Department of Psychiatry, Henan Mental Health Center, Xinxiang, Henan 453002, P.R. China.

出版信息

Mol Med Rep. 2014 Dec;10(6):3247-53. doi: 10.3892/mmr.2014.2638. Epub 2014 Oct 14.

Abstract

Depression is a well‑established risk factor for cardiac morbidity and mortality in patients with coronary artery disease (CAD). Previous studies have demonstrated that the level of brain‑derived neurotrophic factor (BDNF) is decreased in depressed patients and this depletion may be reversed by antidepressants. Several recent studies have suggested that BDNF is involved in the pathogenesis of CAD. The aim of the present study was to investigate the possible association between seven single nucleotide polymorphisms (SNPs) of the BDNF gene (SNPs; rs16917204, rs6265, rs7103873, rs16917237, rs56164415, rs13306221 and rs10767664) and coronary artery disease‑related depression (CAD‑D). In the present study, 616 CAD patients without depression (CAD‑nD) and 155 patients with CAD‑D were recruited, and the response to an eight week sertraline antidepressant treatment regimen was also evaluated. The results demonstrated that a significant association existed between the SNP rs6265, located in exon 4 of the BDNF gene, and CAD‑D [χ2=9.634, P=0.002, odds ratio (OR)=1.486, 95% confidence interval (CI)=1.156‑1.910]. Another potential association was observed for rs13306221 (χ2=5.194, P=0.023, OR=2.139, 95% CI=1.096‑4.175) in the promoter region of the BDNF gene. Strong linkage disequilibrium was observed in block 1 (rs16917204, rs6265; D'>0.9). However, there was no evidence of a significant linkage disequilibrium between the seven SNPs in our sample population. Additionally, carriers of the A allele of rs6265 exhibited improved responses to the sertraline treatment (χ2=8.942, P=0.003, OR=2.136, 95% CI=1.293‑3.528). To the best of our knowledge, these results demonstrate, for the first time, the presence of a significant association between BDNF rs6265 and CAD‑D, the identification of which may facilitate early diagnosis of CAD‑D in the future.

摘要

抑郁症是冠状动脉疾病(CAD)患者发生心脏疾病和死亡的一个公认风险因素。先前的研究表明,抑郁症患者脑源性神经营养因子(BDNF)水平降低,而这种消耗可能会被抗抑郁药逆转。最近的几项研究表明,BDNF参与了CAD的发病机制。本研究的目的是调查BDNF基因的七个单核苷酸多态性(SNP;rs16917204、rs6265、rs7103873、rs16917237、rs56164415、rs13306221和rs10767664)与冠状动脉疾病相关性抑郁症(CAD-D)之间可能存在的关联。在本研究中,招募了616例无抑郁症的CAD患者(CAD-nD)和155例CAD-D患者,并评估了他们对为期八周的舍曲林抗抑郁治疗方案的反应。结果表明,位于BDNF基因外显子4的SNP rs6265与CAD-D之间存在显著关联[χ2=9.634,P=0.002,优势比(OR)=1.486,95%置信区间(CI)=1.156-1.910]。在BDNF基因启动子区域的rs13306221也观察到另一种潜在关联(χ2=5.194,P=0.023,OR=2.139,95%CI=1.096-4.175)。在1号区域(rs16917204、rs6265;D'>0.9)观察到强连锁不平衡。然而,在我们的样本人群中,没有证据表明这七个SNP之间存在显著的连锁不平衡。此外,rs6265的A等位基因携带者对舍曲林治疗的反应有所改善(χ2=8.942,P=0.003,OR=2.136,95%CI=1.293-3.528)。据我们所知,这些结果首次证明了BDNF rs6265与CAD-D之间存在显著关联,这一关联的确定可能有助于未来CAD-D的早期诊断。

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