Alternative titles; symbols
HGNC Approved Gene Symbol: PLTP
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38) : 20:45,898,620-45,912,155 (from NCBI)
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.
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.
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.
Associations Pending Confirmation
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).
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.
This variant, formerly titled HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 9, has been reclassified as a polymorphism. The variant was present in 9,081 of 31,296 alleles and in 1,301 homozygotes, with an allele frequency of 0.2902, in the gnomAD database (v2.1.1) (Hamosh, 2023).
In an association study of 7 HDL metabolism genes in participants in the Dallas Heart Study and in 849 African American men and women from Maywood, IL, Spirin et al. (2007) identified a SNP of the PLTP gene, rs3843763, that was associated with incremental changes in HDL cholesterol levels in 3 independent samples. This SNP achieved a P value of 1.19 x 10(-4) in analysis of covariance in the entire sample in a model that included race, sex, age, and body mass index (BMI). The minor allele, T, was associated with lowering of HDL cholesterol. Spirin et al. (2007) found that the C-T variant of PLTP acts in concert with other SNPs in the CETP (118470.0005) and LPL (609708.0042) genes to affect plasma levels of high density lipoprotein cholesterol.
Day, J. R., Albers, J. J., Lofton-Day, C. E., Gilbert, T. L., Ching, A. F. T., Grant, F. J., O'Hara, P. J., Marcovina, S. M., Adolphson, J. L. Complete cDNA encoding human phospholipid transfer protein from human endothelial cells. J. Biol. Chem. 269: 9388-9391, 1994. [PubMed: 8132678]
Hamosh, A. Personal Communication. Baltimore, Md. 5/18/2023.
Jiang, X., Bruce, C., Mar, J., Lin, M., Ji, Y., Francone, O. L., Tall, A. R. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J. Clin. Invest. 103: 907-914, 1999. [PubMed: 10079112] [Full Text: https://doi.org/10.1172/JCI5578]
LeBoeuf, R. C., Caldwell, M., Tu, A.-Y., Albers, J. J. Phospholipid transfer protein maps to distal mouse chromosome 2. Genomics 34: 259-260, 1996. [PubMed: 8661063] [Full Text: https://doi.org/10.1006/geno.1996.0280]
Spirin, V., Schmidt, S., Pertsemlidis, A., Cooper, R. S., Cohen, J. C., Sunyaev, S. R. Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol. Am. J. Hum. Genet. 81: 1298-1303, 2007. [PubMed: 17952847] [Full Text: https://doi.org/10.1086/522497]
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., Johansen, C. T., Fouchier, S. W., and 197 others. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707-713, 2010. [PubMed: 20686565] [Full Text: https://doi.org/10.1038/nature09270]
Tu, A.-Y., Wolfbauer, G., Albers, J. J. Functional characterization of the promoter region of the human phospholipid transfer protein gene. Biochem. Biophys. Res. Commun. 217: 705-711, 1995. [PubMed: 8554588] [Full Text: https://doi.org/10.1006/bbrc.1995.2830]
Whitmore, T. E., Day, J. R., Albers, J. J. Localization of the human phospholipid transfer protein gene to chromosome 20q12-q13.1. Genomics 28: 599-600, 1995. [PubMed: 7490104] [Full Text: https://doi.org/10.1006/geno.1995.1198]