title: Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia.
abstract: The relevance of apolipoprotein A-V (apoA-V) 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 an LPL-activating role of apoA-V. An inverse correlation between plasma apoA-V and triglyceride (TG) levels has been surmised from animal data. Recent studies in human subjects using (semi)quantitative immunoassays, however, do not provide unambiguous support for such a relationship. Here, we used a novel, validated ELISA to measure plasma apoA-V levels in patients (n = 28) with hypertriglyceridemia (HTG; 1.8-78.7 mmol TG/l) and normolipidemic controls (n = 42). Unexpectedly, plasma apoA-V levels were markedly increased in the HTG subjects compared with controls (1,987 vs. 258 ng/ml; P < 0.001). In the HTG group, apoA-V and TG were positively correlated (r = +0.44, P = 0.02). In addition, we noted an increased level of the LPL-inhibitory protein apoC-III in the HTG group (45.8 vs. 10.6 mg/dl in controls; P < 0.001). The correlation between apoA-V and TG levels in the HTG group disappeared (partial r = +0.09, P = 0.65) when controlling for apoC-III levels. In contrast, apoC-III and TG remained positively correlated in this group when controlling for apoA-V (partial r = +0.43, P = 0.025). Our findings suggest that in HTG patients, increased TG levels are accompanied by high plasma levels of apoA-V and apoC-III, apolipoproteins with opposite modes of action. This study provides evidence for a complex interaction between apoA-V and apoC-III in patients with severe HTG.
authors.affiliation: Academic Medical Center Liver Center, 1105 BK Amsterdam, The Netherlands. f.g.schaap@amc.uva.nl
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.forename: Melchior C
authors.initials: MC
authors.lastname: Nierman
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Stefan F C
authors.initials: SF
authors.lastname: Vaessen
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Robert A F M
authors.initials: RA
authors.lastname: Chamuleau
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
mesh_terms: D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000097:blood*; D001054:Apolipoproteins A / Q000097:blood*; D002138:Calibration; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D014280:Triglycerides