Lipid transfer inhibitor protein (Apolipoprotein F) concentration in normolipidemic and hyperlipidemic subjects

Richard E. Morton, Hannah M. Gnizak, Diane J. Greene, Kyung-Hyun Cho, and Victor M. Paromov

Cell Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH 44195

Corresponding Author: mortonr{at}ccf.org

Lipid transfer inhibitor protein (LTIP) is an important regulator of cholesteryl ester transfer protein function. We report the development of an immunoassay for LTIP and its use to quantify LTIP in plasmas of varying lipid content. A rabbit antibody against bacterially-produced recombinant LTIP detected two LTIP isoforms in plasma, differing in carbohydrate content. This antibody was used in a competitive, enzyme-linked immunoassay employing partially-purified LTIP bound to microtiter plates. To optimize LTIP immunoreactivity, plasma samples required pre-incubation in 1% Tween-20, 0.5% NP-40. In normolipidemic plasma, LTIP averaged 83.5 µg/ml. LTIP was 31% higher in males than females. LTIP was positively associated with HDL cholesterol in normolipidemic males but not females. In hypertriglyceridemic males, LTIP was only 56% of control values, whereas in hypertriglyceridemic females LTIP tended to increase. Additionally, in males with normal cholesterol and triglyceride = 200 mg/dl, LTIP varied inversely with plasma triglyceride. Overall, we have confirmed the negative association between plasma triglyceride levels and LTIP previously suggested by a small data set, but now demonstrate this effect is only seen in males. The mechanisms underlying this gender specific response to triglyceride, and why LTIP and HDL levels correlate in males but not females, remain to be determined.

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