Genetic variation in phospholipid transfer protein modulates lipoprotein profiles in hyperalphalipoproteinemia

• Published in: Metabolism, clinical and experimental Vol. 57; no. 12; pp. 1719 - 1724
• Main Authors: Engler, Mary B., Pullinger, Clive R., Malloy, Mary J., Natanzon, Yanina, Kulkarni, Medha V., Song, James, Eng, Celeste, Huuskonen, Jaarko, Rivera, Christopher, Poon, Annie, Bensley, Matt, Sehnert, Amy, Zellner, Christian, Kane, John, Aouizerat, Bradley E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2008; Elsevier
• Subjects: Adult; Aged; Animals; Biological and medical sciences; Case-Control Studies; Chlorocebus aethiops; COS Cells; Disorders of blood lipids. Hyperlipoproteinemia; Endocrinology & Metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Genetic Variation - physiology; Humans; Hyperlipoproteinemias - blood; Hyperlipoproteinemias - genetics; Lipoproteins - blood; Lipoproteins, HDL - blood; Male; Medical sciences; Metabolic diseases; Middle Aged; Phospholipid Transfer Proteins - genetics; Retrospective Studies; Transfection; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Phospholipid; Variations; Metabolic diseases; Lipids; Hyperlipoproteinemia; Dyslipemia; Lipoprotein HDL; Endocrinology; Hyperalphalipoproteinemia; Protein; Genetic transfer
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2008.07.031

We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.