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Journal of Lipid Research, Vol. 49, 127-135, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

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

Richard E. Morton¹, Hannah M. Gnizak, Diane J. Greene, Kyung-Hyun Cho² and Victor M. Paromov³

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

Published, JLR Papers in Press, September 27, 2007.

² Present address of K-H. Cho: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, South Korea.

³ Present address of V. M. Paromov: Department of Pediatrics, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

¹ To whom correspondence should be addressed. e-mail: 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 plasma of varying lipid contents. 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 that uses partially purified LTIP bound to microtiter plates. To optimize LTIP immunoreactivity, plasma samples required preincubation in 1% Tween-20 and 0.5% Nonidet P-40. In normolipidemic plasma, LTIP averaged 83.5 µg/ml. LTIP was 31% higher in males than in females. LTIP was positively associated with HDL cholesterol in normolipidemic males but not in 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 (TG) 200 mg/dl, LTIP varied inversely with plasma TG. Overall, we have confirmed the negative association between plasma TG levels and LTIP previously suggested by a small data set, but now we demonstrate that this effect is seen only in males. The mechanisms underlying this gender-specific response to TG, and why LTIP and HDL levels correlate in males but not in females, remain to be determined.

Supplementary key words cholesteryl ester transfer protein • cholesteryl ester transfer protein inhibition • glycoprotein • enzyme-linked immunosorbent assay

Abbreviations: CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; LTIP, lipid transfer inhibitor protein; NANase, N-acetylneuraminidase; rLTIP, recombinant lipid transfer inhibitor protein; TG, triglyceride

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