The role of genetically-influenced phospholipid transfer protein activity in lipoprotein metabolism and coronary artery disease

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY Journal of clinical lipidology Pub Date : 2024-07-01 DOI:10.1016/j.jacl.2024.03.007

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Abstract

BACKGROUND

Phospholipid transfer protein (PLTP) transfers surface phospholipids between lipoproteins and as such plays a role in lipoprotein metabolism, but with unclear effects on coronary artery disease (CAD) risk. We aimed to investigate the associations of genetically-influenced PLTP activity with 1-H nuclear magnetic resonance (¹H-NMR) metabolomic measures and with CAD. Furthermore, using factorial Mendelian randomization (MR), we examined the potential additional effect of genetically-influenced PLTP activity on CAD risk on top of genetically-influenced low-density lipoprotein-cholesterol (LDL-C) lowering.

METHODS

Using data from UK Biobank, genetic scores for PLTP activity and LDL-C were calculated and dichotomised based on the median, generating four groups with combinations of high/low PLTP activity and high/low LDL-C levels for the factorial MR. Linear and logistic regressions were performed on 168 metabolomic measures (N = 58,514) and CAD (N = 318,734, N-cases=37,552), respectively, with results expressed as β coefficients (in standard deviation units) or odds ratios (ORs) and 95% confidence interval (CI).

RESULTS

Irrespective of the genetically-influenced LDL-C, genetically-influenced low PLTP activity was associated with a higher high-density lipoprotein (HDL) particle concentration (β [95% CI]: 0.03 [0.01, 0.05]), smaller HDL size (-0.14 [-0.15, -0.12]) and higher triglyceride (TG) concentration (0.04 [0.02, 0.05]), but not with CAD (OR 0.99 [0.97, 1.02]). In factorial MR analyses, genetically-influenced low PLTP activity and genetically-influenced low LDL-C had independent associations with metabolomic measures, and genetically-influenced low PLTP activity did not show an additional effect on CAD risk.

CONCLUSIONS

Low PLTP activity associates with higher HDL particle concentration, smaller HDL particle size and higher TG concentration, but no association with CAD risk was observed.

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受基因影响的磷脂转移蛋白活性在脂蛋白代谢和冠心病中的作用

背景磷脂转移蛋白（PLTP）在脂蛋白之间转移表面磷脂，因此在脂蛋白代谢中发挥作用，但对冠状动脉疾病（CAD）风险的影响尚不明确。我们的目的是研究受基因影响的 PLTP 活性与 1-H 核磁共振 (1H-NMR) 代谢组学指标以及与冠心病的关系。方法利用英国生物样本库的数据，计算 PLTP 活性和 LDL-C 的遗传评分，并根据中位数进行二分，在因子 MR 中生成高/低 PLTP 活性和高/低 LDL-C 水平组合的四个组。分别对 168 个代谢组测量值（样本数=58,514）和 CAD（样本数=318,734，病例数=37,552）进行线性回归和逻辑回归，结果以 β 系数（标准差单位）或几率比（OR）和 95% 置信区间（CI）表示。结果与受基因影响的 LDL-C 无关，受基因影响的低 PLTP 活性与较高的高密度脂蛋白（HDL）颗粒浓度相关（β [95% CI]: 0.03 [0.01, 0.05]）、HDL 粒径较小（-0.14 [-0.15, -0.12]）和甘油三酯（TG）浓度较高（0.04 [0.02, 0.05]）有关，但与 CAD 无关（OR 0.99 [0.97, 1.02]）。在因子MR分析中，受基因影响的低PLTP活性和受基因影响的低LDL-C与代谢组学指标有独立的关联，而受基因影响的低PLTP活性对CAD风险没有额外的影响。

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

Journal of clinical lipidology 医学-药学

CiteScore

7.00

自引率

6.80%

发文量

209

审稿时长

49 days

期刊介绍： Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. While preference is given to material of immediate practical concern, the science that underpins lipidology is forwarded by expert contributors so that evidence-based approaches to reducing cardiovascular and coronary heart disease can be made immediately available to our readers. Sections of the Journal will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.