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
{"title":"The role of genetically-influenced phospholipid transfer protein activity in lipoprotein metabolism and coronary artery disease","authors":"","doi":"10.1016/j.jacl.2024.03.007","DOIUrl":null,"url":null,"abstract":"<div><h3>BACKGROUND</h3><p>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 (<sup>1</sup>H-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.</p></div><div><h3>METHODS</h3><p>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 (<em>N</em> = 58,514) and CAD (<em>N</em> = 318,734, N-cases=37,552), respectively, with results expressed as <em>β</em> coefficients (in standard deviation units) or odds ratios (ORs) and 95% confidence interval (CI).</p></div><div><h3>RESULTS</h3><p>Irrespective of the genetically-influenced LDL-C, genetically-influenced low PLTP activity was associated with a higher high-density lipoprotein (HDL) particle concentration (<em>β</em> [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.</p></div><div><h3>CONCLUSIONS</h3><p>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.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e579-e587"},"PeriodicalIF":3.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933287424000436/pdfft?md5=b171e8f09e2e29fe1ddb0b0aec5ec584&pid=1-s2.0-S1933287424000436-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933287424000436","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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。
求助全文
约1分钟内获得全文 去求助
来源期刊
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.
期刊最新文献
Burden of atherogenic lipids and association with cardiac allograft vasculopathy in heart transplant recipients. Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America. Identification and functional analysis of novel homozygous LMF1 variants in severe hypertriglyceridemia. Falsely elevated triglyceride and lipase levels due to hyperglycerolemia in a burn patient treated with topical silver sulfadiazine. Complex dyslipidemia induced by Lorlatinib therapy: A case study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1