Exploring the impact of metabolites function on heart failure and coronary heart disease: insights from a Mendelian randomization (MR) study.

IF 1.3 American journal of cardiovascular disease Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI:10.62347/OQXZ7740
Vicheth Virak, Pengkhun Nov, Deshu Chen, Xuwei Zhang, Junjie Guan, Dongdong Que, Jing Yan, Vanna Hen, Senglim Choeng, Chongbin Zhong, Pingzhen Yang
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Abstract

Background: Heart failure (HF) and coronary heart disease (CHD) are major causes of morbidity and mortality worldwide. While traditional risk factors such as hypertension, diabetes, and smoking have been extensively studied, the role of metabolite functions in the development of these cardiovascular conditions has been less explored. This study employed a Mendelian randomization (MR) approach to investigate the impact of metabolite functions on HF and CHD.

Methods: To assess the causal impacts of specific metabolite risk factors on HF and CHD, this study utilized genetic variants associated with these factors as instrumental variables. Comprehensive genetic and phenotypic data from diverse cohorts, including genome-wide association studies (GWAS) and cardiovascular disease registries, were incorporated into the research.

Results: Our results encompass 61 metabolic cell phenotypes, with ten providing strong evidence of the influence of metabolite functions on the occurrence of HF and CHD. We found that elevated levels of erucate (22:1n9), lower levels of α-tocopherol, an imbalanced citrulline-to-ornithine ratio, elevated γ-glutamyl glycine levels, and elevated 7-methylguanine levels independently increased the risk of these cardiovascular conditions. These findings were consistent across different populations and robust to sensitivity analyses.

Conclusion: This MR study provides valuable insights into the influence of metabolite functions on HF and CHD. However, further investigation is needed to fully understand the precise mechanisms by which these metabolite factors contribute to the onset of these conditions. Such research could pave the way for the development of targeted therapeutic strategies.

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探索代谢物功能对心力衰竭和冠心病的影响:孟德尔随机化(MR)研究的启示。
背景:心力衰竭(HF)和冠心病(CHD)是全球发病率和死亡率的主要原因。虽然高血压、糖尿病和吸烟等传统风险因素已被广泛研究,但代谢物功能在这些心血管疾病发病过程中的作用却较少被探讨。本研究采用孟德尔随机化(MR)方法研究代谢物功能对高血压和冠心病的影响:为了评估特定代谢物风险因素对高血压和冠心病的因果影响,本研究利用与这些因素相关的遗传变异作为工具变量。研究纳入了来自不同队列的综合遗传和表型数据,包括全基因组关联研究(GWAS)和心血管疾病登记:我们的研究结果包括 61 种代谢细胞表型,其中 10 种表型提供了代谢物功能对高血压和冠心病发生影响的有力证据。我们发现,芥酸盐(22:1n9)水平升高、α-生育酚水平降低、瓜氨酸与鸟氨酸比率失衡、γ-谷氨酰甘氨酸水平升高和 7-甲基鸟嘌呤水平升高会独立增加这些心血管疾病的风险。这些研究结果在不同人群中是一致的,而且对敏感性分析也是可靠的:这项磁共振研究为了解代谢物功能对高血压和冠心病的影响提供了宝贵的见解。结论:这项磁共振研究为了解代谢物功能对高血压和冠心病的影响提供了有价值的见解。然而,要充分了解这些代谢物因素导致这些疾病发生的确切机制,还需要进一步的研究。此类研究可为开发有针对性的治疗策略铺平道路。
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来源期刊
American journal of cardiovascular disease
American journal of cardiovascular disease CARDIAC & CARDIOVASCULAR SYSTEMS-
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发文量
21
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