HUMAN MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN LARGE SUBUNIT GENE STRUCTURE

Microsomal triglyceride transfer protein (MTP) is a heterodimer consis ting of the multifunctional enzyme protein disulfide isomerase and a u nique, large 97-kDa subunit. MTP is required for the assembly and secr etion of very low density lipoproteins and chylomicrons by the liver a nd intestine, respectively. In vitro, MTP catalyzes the transport of t riglyceride, cholesteryl ester, and phosphatidylcholine between phosph olipid surfaces. We have characterized the gene encoding the large sub unit of human MTP. It contains 18 exons and spans approximately 55-60 kb. Fluorescent in situ hybridization localized this gene to band 4q24 of chromosome 4. A (CA)(n) repeat polymorphic marker, which may be us eful for investigating a link between the MTP gene and genetic defects in lipid metabolism, was identified in intron 10. Sequence analysis o f the 5' flanking region of the gene revealed potential sites which ma y bind transcriptional factors and control MTP expression.