Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding.

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.

The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA52, and their paradoxical association with plasma triglyceride but not plasma apoAV levels.

Plasma triglyceride (TG) and apoAV levels are reported to be positively correlated, yet SNPs defining haplotype APOA52 have consistently shown association with elevated plasma triglyceride (TG) but not plasma apoAV levels. We previously reported that individually -1131T>C, -3A>G and +1891T>C did not influence luciferase activity or in vitro translation efficiency. To investigate the combined effect of these SNPs additional constructs were examined.

The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes.

Common variants in APOA5 and APOC3 have been associated with differences in plasma triglyceride (TG) levels in healthy individuals. The aim of this study was to examine the association of APOA5 (-1131T>C, S19W) and APOC3 (-482C>T, 1100C>T) polymorphisms in patients with type 2 diabetes (T2D) of European White (EW) (n=931), Indian Asian (IA) (n=610) and Afro-Caribbean (AC) (n=167) origin, with lipid and T2D parameters. Rare allele frequencies and linkage disequilibrium differed significantly amongst ethnic groups.

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats.

Aims/hypothesis: Apolipoprotein AV (apoAV) is a recently discovered apolipoprotein with a triglyceride-lowering effect in genetically modified mice. Transcription of the human gene encoding apoAV (APOA5) is suppressed by insulin and stimulated by fibrates. Our goal was to study the expression of Apoa5, in comparison with Apoa4 and Apoc3, in hypertriglyceridaemic, obese and insulin-resistant Zucker rats receiving the insulin sensitiser rosiglitazone and/or a fish oil diet to lower triglycerides.