Phospholipid Transfer Protein

Cloning and Expression

Human plasma contains at least 2 different lipid transfer proteins: cholesteryl ester transfer protein (118470), also referred to as lipid transfer protein I, and phospholipid transfer protein (PLTP), also referred to as lipid transfer protein II. Day et al. (1994) purified phospholipid transfer protein with an apparent molecular mass of 81 kD from human plasma. From the NH2-terminal amino acid sequence, they designed primers for polymerase chain reaction and isolated a full-length cDNA from a human endothelial cDNA library. The cDNA was 1,750 bp long and contained an open reading frame of 1,518 nucleotides encoding a leader of 17 amino acids and a mature protein of 476 residues.

Gene Function

Tu et al. (1995) identified the functional promoter of the PLTP gene. The promoter consists of a TATA box, a high-GC content region, and several consensus sequences for the potential binding of transcription factors. A minimal promoter of 159 bp between -230 and -72 relative to the first transcriptional initiation site was responsible for the full activity. Two transcription factor-binding motifs, SP1 and AP-2, are located within this area. It appeared that the PLTP promoter activity relies primarily on the putative cis-elements in the functional region.

Mapping

Using a human/rodent somatic cell hybrid mapping panel, Day et al. (1994) mapped the PLTP gene to chromosome 20. Whitmore et al. (1995) narrowed the assignment to 20q12-q13.1 by fluorescence in situ hybridization. LeBoeuf et al. (1996) demonstrated that the Pltp gene maps to the distal portion of mouse chromosome 2.

Molecular Genetics

In an evaluation of the hypothesis that multiple high density lipoprotein cholesterol (HDL-C) levels reflect the cumulative contributions of multiple common DNA sequence variants, each of which has a small effect, Spirin et al. (2007) identified a single-nucleotide polymorphism (SNP) of the PLTP gene (172425.0001) that acts in concert with other SNPs in the CETP (118470.0005) and LPL (118470.0042) genes to affect plasma levels of high density lipoprotein cholesterol.

In a metaanalysis of plasma lipid concentrations in greater than 100,000 individuals of European descent, Teslovich et al. (2010) identified rs6065906 near the PLTP gene as having an effect on HDL cholesterol concentrations as well as triglyceride with an effect size of -0.93 mg per deciliter and a P value of 2 x 10(-22).

Animal Model

Using homologous recombination in embryonic stem cells, Jiang et al. (1999) produced mice with no PLTP gene expression. Reduced plasma PLTP activity caused markedly decreased high density lipoprotein (HDL) lipid and apoprotein, demonstrating the importance of transfer surface components of triglyceride-rich lipoproteins in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP -/- mice on a high-fat diet could influence the development of atherosclerosis.