| Title: | The role of genetically-influenced phospholipid transfer protein activity in lipoprotein metabolism and coronary artery disease |
| Journal: | Journal of Clinical Lipidology |
| Published: | 29 Mar 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38906750/ |
| DOI: | https://doi.org/10.1016/j.jacl.2024.03.007 |
| URL: | http://www.lipidjournal.com/article/S1933287424000436/pdf |
Publication 10157
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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.</p>
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).</p>
RESULTS: Irrespective of the genetically-influenced LDL-C, genetically-influenced low PLTP activity was associated with a higher 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.</p>
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.</p>
5 Authors
- Linjun Ao
- Raymond Noordam
- Patrick C N Rensen
- Diana van Heemst
- Ko Willems van Dijk
1 Application
| Application ID | Title |
|---|---|
| 27412 | Boosting the power of GWAS using novel statistical tools |
Enabling scientific discoveries that improve human health