Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 37, Issue 1, Pages 43-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.116.307995
Keywords
lipoprotein(a); lipoproteins; nuclear magnetic resonance spectroscopy; PCSK9; R46L
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Funding
- Cancer Research UK [14136]
- Medical Research Council [G1000143]
- European Union [FP7-603091-2]
- Fonds de recherche du Quebec: Sante (FRQS)
- Dutch Heart Foundation Lifetime Achievement Award
- Medical Research Council [MC_U106179471, MC_PC_13048, MC_UU_12015/1, MR/N003284/1, G0401527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114] Funding Source: researchfish
- MRC [MR/N003284/1, MC_UU_12015/1] Funding Source: UKRI
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Objective-Carriers of the PCSK9 (proprotein convertase subtilisin/kexin 9) R46L genetic variant (rs11591147) are characterized by low levels of low-density lipoprotein cholesterol and a decreased risk of cardiovascular disease. We studied the impact of the R46L variant on lipoprotein size and composition. Approach and Results-Lipoprotein size and composition were measured by nuclear magnetic resonance spectroscopy in 2373 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. After adjusting for age, sex, and cardiovascular disease status, carriers of the R46L variant (n=77) were characterized by lower concentrations of very low-density lipoprotein particles (85.8+/-26.2 versus 99.0+/-33.3 nmol/L; P<0.001), low-density lipoprotein particles (1479.7+/-396.8 versus 1662.9+/-458.3 nmol/L; P<0.001), and lipoprotein(a) (11.1 [7.2-28.6] versus 12.4 [6.7-29.1] mg/dL; P<0.001) compared with noncarriers. Total high-density lipoprotein particle and very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particle sizes were comparable in carriers and noncarriers. Carriers were characterized by lower secretory phospholipase A2 (4.2+/-0.9 versus 4.6+/-1.3 nmol/mL/min; P=0.004) and lipoprotein-associated phospholipase A2 activity (47.5+/-14.1 versus 52.4+/-16.2 nmol/mL/min; P=0.02) compared with noncarriers. Conclusions-Results of this study suggest that carriers of the PCSK9 R46L genetic variant have lower very low-density lipoprotein and low-density lipoprotein particle concentrations, lower lipoprotein(a) levels, and lower secretory phospholipase A2 and lipoprotein-associated phospholipase A2 activity compared with noncarriers.
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