| Title: | Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses |
| Journal: | Journal of Lipid Research |
| Published: | 10 Mar 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35278410/ |
| DOI: | https://doi.org/10.1016/j.jlr.2022.100193 |
| URL: | http://www.jlr.org/article/S0022227522000268/pdf |
| Citations: | 4 (2 in last 2 years) as of 8 Aug 2024 |
Publication 12481
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73-0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.</p>
7 Keywords
- Apolipoprotein A-V
- Apolipoproteins A
- Cholesterol, LDL
- Coronary Artery Disease
- Humans
- Lipoproteins
- Triglycerides
12 Authors
- Dorina Ibi
- Manon Boot
- Martijn E.T. Dollé
- J. Wouter Jukema
- Frits R. Rosendaal
- Constantinos Christodoulides
- Matt J. Neville
- Robert Koivula
- Patrick C.N. Rensen
- Fredrik Karpe
- Raymond Noordam
- Ko Willems van Dijk
1 Application
| Application ID | Title |
|---|---|
| 56340 | Prevention of myocardial infarction and primary atherogenic cardiovascular disease from a sex-specific life course perspective |
Enabling scientific discoveries that improve human health