Evidence for a complex relationship between apoAV and apoCIII in patients with severe hypertriglyceridemia

Frank G. Schaap, Melchior C. Nierman, Jimmy F. P. Berbee, Hiroaki Hattori, Philippa J. Talmud, Stefan F. C. Vaessen, Patrick C. N. Rensen, Robert A. F. M. Chamuleau, Jan Albert Kuivenhoven, and Albert K. Groen

AMC Liver Center, Amsterdam 1105 BK

Corresponding Author: f.g.schaap{at}amc.uva.nl

The relevance of apoAV for human lipid homeostasis is underscored by genetic association studies and the identification of truncation-causing mutations in the APOA5 gene as a cause of type V hyperlipidemia, compatible with a lipoprotein lipase (LPL)-activating role of apoAV. An inverse correlation between plasma apoAV and triglyceride (TG) levels has been surmised from animal data. Recent studies in human subjects employing (semi)quantitative immunoassays, however, do not provide unambiguous support for such relationship. We here employed a novel, validated ELISA to measure plasma apoAV levels in patients (n=28) with hypertriglyceridemia (HTG; 1.8–78.7 mmol TG/l) and normolipidemic controls (n=42). Unexpectedly, plasma apoAV levels were markedly elevated in the HTG subjects compared to controls (1987 vs. 258 ng/ml; p<0.001). In the HTG group, apoAV and TG were positively correlated (r=+0.44, p=0.02). In addition, we noted an increased level of the LPL-inhibitory protein apoCIII in the HTG group (45.8 vs. 10.6 mg/dl in controls; p<0.001). The correlation between apoAV and TG levels in the HTG group disappeared (partial r=+0.09, p=0.65) when controlling for apoCIII levels. In contrast, apoCIII and TG remained positively correlated in this group when controlling for apoAV (partial r=+0.43, p=0.025). Our findings suggest that in HTG patients, elevated TG levels are accompanied by elevated plasma levels of apoAV and apoCIII, apolipoproteins with opposite modes of action. This study provides evidence for a complex interaction between apoAV and apoCIII in patients with severe hypertriglyceridemia.

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