Reference : Effects Of Six Apoa5 Variants, Identified In Patients With Severe Hypertriglyceridemi...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/65784
Effects Of Six Apoa5 Variants, Identified In Patients With Severe Hypertriglyceridemia, On In Vitro Lipoprotein Lipase Activity And Receptor Binding
English
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 mailto [Université de Liège > > Gembloux Agro-Bio Tech >]
Delsaux, N. [> > > >]
Nierman, M. [> > > >]
Kuivenhoven, Ja. [> > > >]
Kastelein, Jjp. [> > > >]
Vrablik, M. [> > > >]
Olivecrona, G. [> > > >]
Schneider, Wj. [> > > >]
Heeren, J. [> > > >]
Humphries, Se. [> > > >]
Talmud, Pj. [> > > >]
2008
Arteriosclerosis, Thrombosis, and Vascular Biology
28
10
1866-71
Yes (verified by ORBi)
International
1079-5642
[en] 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 -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant. CONCLUSIONS: The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.
Researchers ; Professionals
http://hdl.handle.net/2268/65784
10.1161/ATVBAHA.108.172866

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
68.pdfNo commentaryPublisher postprint639.79 kBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.