{"title":"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","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":null,"pages":null},"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":"{\"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\":null,\"pages\":null},\"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}","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}
The role of genetically-influenced phospholipid transfer protein activity in lipoprotein metabolism and coronary artery disease
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.
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.
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