The Causal Effect of Serum Lipid Levels Mediated by Neuregulin 4 on the Risk of Four Atherosclerosis Subtypes: Evidence from Mendelian Randomization Analysis.

IF 2.6 Q2 PERIPHERAL VASCULAR DISEASE

Vascular Health and Risk Management Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI:10.2147/VHRM.S459075

Longyi Zheng, Chengjing Zhang, Shichang Bu, Wencheng Guo, Tongtong Li, Ying Xu, Yunan Liu, Caimei Yuan, Chengwu Feng, Geng Zong, Jingwen Zhu, Maoying Xing, Xin Geng

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引用次数: 0

Abstract

Background: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.

Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance-weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.

Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.

Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.

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Neuregulin 4介导的血清脂质水平对四种动脉粥样硬化亚型风险的因果效应：孟德尔随机分析的证据

背景：已知神经胶质蛋白4（NRG4）与血清脂质水平和动脉粥样硬化有关。然而，NRG4在血脂平衡中的作用是否与动脉粥样硬化有因果关系，以及这种作用在不同动脉粥样硬化亚型中是否有益，目前尚不清楚：我们通过双样本孟德尔随机法研究了NRG4调节的血清低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇和甘油三酯水平在动脉粥样硬化亚型中的因果作用。全球血脂遗传学联合会（Global Lipids Genetics Consortium）提供了 132 万欧洲血统个体血清血脂水平的全基因组关联研究（GWAS）汇总数据。四种动脉粥样硬化亚型（外周动脉粥样硬化、冠状动脉粥样硬化、脑动脉粥样硬化和其他动脉粥样硬化）的全基因组关联研究汇总数据来自 FinnGen Consortium。采用广义逆方差加权孟德尔随机法和几种敏感性分析来获得因果关系估计值：结果：NRG4介导的1-SD遗传性低密度脂蛋白胆固醇水平升高被证实与外周动脉粥样硬化风险有名义上的关联（对数（几率比）= 4.14，95%置信区间为0.11至8.17，P = 0.04），其他关联不显著或无法通过敏感性分析得到证实：结论：NRG4介导的低密度脂蛋白胆固醇降低可能会预防外周动脉粥样硬化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vascular Health and Risk Management PERIPHERAL VASCULAR DISEASE-

CiteScore

4.20

自引率

3.40%

发文量

109

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed journal of therapeutics and risk management, focusing on concise rapid reporting of clinical studies on the processes involved in the maintenance of vascular health; the monitoring, prevention, and treatment of vascular disease and its sequelae; and the involvement of metabolic disorders, particularly diabetes. In addition, the journal will also seek to define drug usage in terms of ultimate uptake and acceptance by the patient and healthcare professional.