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血管内皮生长因子(VEGF)通路中生化和遗传生物标志物与抑郁症的关联

The Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression.

作者信息

Nunes Fernanda Daniela Dornelas, Ferezin Letícia Perticarrara, Pereira Sherliane Carla, Figaro-Drumond Fernanda Viana, Pinheiro Lucas Cézar, Menezes Itiana Castro, Baes Cristiane von Werne, Coeli-Lacchini Fernanda Borchers, Tanus-Santos José Eduardo, Juruena Mário Francisco, Lacchini Riccardo

机构信息

Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil.

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paolo 14049-900, Brazil.

出版信息

Pharmaceutics. 2022 Dec 9;14(12):2757. doi: 10.3390/pharmaceutics14122757.

Abstract

VEGF is an important neurotrophic and vascular factor involved in mental disorders. The objective of this study was to verify the effect of genetic polymorphisms in the VEGF pathway on the risk for depression, symptom intensity, and suicide attempts. To examine the association between the VEGF pathway and depression, we genotyped polymorphisms and measured the plasma concentrations of VEGF, KDR, and FLT1 proteins. The participants were 160 patients with depression and 114 healthy controls. The questionnaires that assessed the clinical profile of the patients were the MINI-International Neuropsychiatric Interview, GRID-HAMD, CTQ, BSI, and the number of suicide attempts. Genotyping of participants was performed using the real-time PCR and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). VEGF and its inhibitors were reduced in depression. Individuals with depression and displaying the homozygous AA of the rs699947 polymorphism had higher plasma concentrations of VEGF (-value = 0.006) and were associated with a greater number of suicide attempts (-value = 0.041). Individuals with depression that were homozygous for the G allele of the FLT1 polymorphism rs7993418 were associated with lower symptom severity (-value = 0.040). Our results suggest that VEGF pathway polymorphisms are associated with the number of suicide attempts and the severity of depressive symptoms.

摘要

血管内皮生长因子(VEGF)是一种参与精神障碍的重要神经营养和血管因子。本研究的目的是验证VEGF通路中的基因多态性对抑郁症风险、症状强度和自杀未遂的影响。为了研究VEGF通路与抑郁症之间的关联,我们对多态性进行了基因分型,并测量了VEGF、激酶插入结构域受体(KDR)和fms样酪氨酸激酶1(FLT1)蛋白的血浆浓度。参与者为160例抑郁症患者和114名健康对照者。评估患者临床特征的问卷包括简明国际神经精神访谈量表(MINI)、汉密尔顿抑郁量表(GRID-HAMD)、儿童创伤问卷(CTQ)、症状自评量表(BSI)以及自杀未遂次数。使用实时聚合酶链反应(PCR)对参与者进行基因分型,并使用酶联免疫吸附测定(ELISA)进行蛋白质测量。抑郁症患者体内的VEGF及其抑制剂水平降低。患有抑郁症且表现为rs699947多态性纯合子AA的个体,其VEGF血浆浓度较高(P值=0.006),且与更多的自杀未遂次数相关(P值=0.041)。FLT1多态性rs7993418的G等位基因纯合的抑郁症患者,其症状严重程度较低(P值=0.040)。我们的结果表明,VEGF通路多态性与自杀未遂次数和抑郁症状严重程度相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4515/9785844/390d748bc002/pharmaceutics-14-02757-g001.jpg

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