[Corrections added on 15 July 2013, after first online publication: Author's name was corrected to reflect correct spelling.].
Two novel mutations in apolipoprotein C3 underlie atheroprotective lipid profiles in families
Article first published online: 24 JUN 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 85, Issue 5, pages 433–440, May 2014
How to Cite
Bochem, A.E., van Capelleveen, J.C., Dallinga-Thie, G.M., Schimmel, A.W.M., Motazacker, M.M., Tietjen, I., Singaraja, R.R., Hayden, M.R., Kastelein, J.J.P., Stroes, E.S.G. and Hovingh, G.K. (2014), Two novel mutations in apolipoprotein C3 underlie atheroprotective lipid profiles in families. Clinical Genetics, 85: 433–440. doi: 10.1111/cge.12201
A. E. B. and M. M. M. are supported by a grant from the Leducq Foundation. J. C. C., G. M. D. and A. W. M. do not have conflicts of interest. I. T. and R. S, have been employed by Xenon Pharmaceuticals Inc. M. R. H. is on the Board of Directors of Xenon Pharmaceuticals Inc. J. J. P. is a recipient of The lifetime Achievement Award of The Dutch Heart Foundation (2011, the Hague, the Netherlands) and has received consultancy fees from Eli-Lilly, BMS, MSD, Roche, Novartis, Isis, Genzyme, Boehringer Ingelheim, Cerenis and Sanofi. E. S. G. has received speaking fees from ISIS pharmaceuticals, BMS, MSD (all minor). G. K. H. is recipient of a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research (NOW) the Hague, the Netherlands. No potential conflicts exist for any of the authors.
- Issue published online: 1 APR 2014
- Article first published online: 24 JUN 2013
- Accepted manuscript online: 22 MAY 2013 01:29PM EST
- Manuscript Revised: 17 MAY 2013
- Manuscript Accepted: 17 MAY 2013
- Manuscript Received: 15 MAR 2013
- Dutch Heart Foundation. Grant Number: 2009B027
- apolipoprotein CIII;
- cardiovascular disease;
- genetic dyslipidemia;
- high-density lipoprotein cholesterol;
Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c.-13-2A>G and c.55+1G>A) and one known mutation (c.127G>A;p.Ala43Thr) were found. Lipid profiles and apoCIII isoform distributions were measured. c.55+1G>A mutation carriers displayed higher HDL-C percentiles (35.6 ± 35.8 vs 99.0 ± 0, p = 0.002) and lower TGs (0.51 (0.37–0.61) vs 1.42 (1.12–1.81) mmol/l, p = 0.007) and apoCIII levels (4.24 ± 1.57 vs 7.33 ± 3.61 mg/dl, p = 0.18). c.-13-2A>G mutation carriers did not display significantly different HDL-C levels (84.0 ± 30.0 vs 63.7 ± 45.7, p = 0.50), a trend towards lower TGs [0.71 (0.54 to 0.78) vs 0.85 (0.85 to –) mmol/l, p = 0.06] and significantly lower apoCIII levels (3.09 ± 1.08 vs 11.45 ± 1.06 mg/dl, p = 0.003). p.Ala43Thr mutation carriers displayed a trend towards higher HDL-C percentiles (91.2 ± 31.8 vs 41.0 ± 29.7 mmol/l, p = 0.06) and significantly lower TGs [0.58 (0.36–0.63) vs 0.95 (0.71–1.20) mmol/l, p = 0.02] and apoCIII levels (4.92 ± 2.33 vs 6.60 ± 1.60, p = 0.25). Heterozygosity for APOC3 mutations results in high HDL-C and low TGs and apoCIII levels. This favourable lipid profile in patients with genetically low apoCIII levels holds promise for current studies investigating the potential of apoCIII inhibition as a novel therapeutic in cardiovascular disease prevention.