Dataset Information

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

ABSTRACT:

Background

The prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.

Methods

A total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.

Results

The BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.

Conclusions

Gene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

SUBMITTER: Kim JM

PROVIDER: S-EPMC6936775 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

Kim Jae-Min JM Stewart Robert R Kim Seon-Young SY Kim Ju-Wan JW Kang Hee-Ju HJ Lee Ju-Yeon JY Kim Sung-Wan SW Shin Il-Seon IS Kim Min Chul MC Hong Young Joon YJ Ahn Youngkeun Y Jeong Myung Ho MH Yoon Jin-Sang JS

PloS one 20191230 12

<h4>Background</h4>The prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.<h4>Methods</h4> ...[more]

PMID: 31887219

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Project description:Most growth factors are initially synthesized as precursors then cleaved into bioactive mature domains and pro-domains, but the biological roles of pro-domains are poorly understood. In the present study, we investigated the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post-processing product of the precursor BDNF. Using surface plasmon resonance and biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to mature BDNF with high affinity, but not other neurotrophins. This interaction was more enhanced at acidic pH than at neutral pH, suggesting that the binding is significant in intracellular compartments such as trafficking vesicles rather than the extracellular space. The common Val66Met BDNF polymorphism results in a valine instead of a methionine in the pro-domain, which affects human brain functions and the activity-dependent secretion of BDNF. We investigated the influence of this variation on the interaction between BDNF and the pro-peptide. Interestingly, the Val66Met polymorphism stabilized the heterodimeric complex of BDNF and its pro-peptide. Furthermore, compared with the Val-containing pro-peptide, the complex with the Met-type pro-peptide was more stable at both acidic and neutral pH, suggesting that the Val66Met BDNF polymorphism forms a more stable complex. A computational modeling provided an interpretation to the role of the Val66Met mutation in the interaction of BDNF and its pro-peptide. Lastly, we performed electrophysiological experiments, which indicated that the BDNF pro-peptide, when pre-incubated with BDNF, attenuated the ability of BDNF to inhibit hippocampal long-term depression (LTD), suggesting a possibility that the BDNF pro-peptide may interact directly with BDNF and thereby inhibit its availability. It was previously reported that the BDNF pro-domain exerts a chaperone-like function and assists the folding of the BDNF protein. However, our results suggest a new role for the BDNF pro-domain (or pro-peptide) following proteolytic cleave of precursor BDNF, and provide insight into the Val66Met polymorphism.

Project description:The val(66)met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people.The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke.Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement.Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present.The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting.

Dataset Information

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

Background

Methods

Results

Conclusions

Publications

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

Similar Datasets

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