Effects Of Six Apoa5 Variants, Identified In Patients With Severe Hypertriglyceridemia, On In Vitro Lipoprotein Lipase Activity And Receptor Binding
- Dorfmeister, B.
- Zeng, Ww.
- Dichlberger, A.
- Nilsson, Sk.
- Schaap, Fg.
- Hubacek, Ja.
- Merkel, M.
- Cooper, Ja.
- Lookene, A.
- Putt, W.
- Whittall, R.
- Lee, Pj.
- Lins, Laurence
- Delsaux, N.
- Nierman, M.
- Kuivenhoven, Ja.
- Kastelein, Jjp.
- Vrablik, M.
- Olivecrona, G.
- Schneider, Wj.
- Heeren, J.
- Humphries, Se.
- Talmud, Pj.
DOIAbstract
OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C27...
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